Formation of dioxin analogs by open-air incineration of waste wood and by fire of buildings and houses concerning Hanshin Great Earthquake in Japan.
Ash samples were collected from site of open-air incineration and fire concerning Hanshin Great Earthquake which occurred in western Japan in the early morning of 17 January 1995. The average concentrations of total sum of PCDDs, PCDFs and Co-PCBs in ash collected from wood scrap of broken building fire site, house fire site, shoe-making factory fire site and electric appliances store fire site were 541, 442, 859 and 22,800 pgTEQ/g, respectively. Particularly, PCDFs among dioxin analogs generated remarkably at sites with a high TEQ. In addition, 79,000 t of ash was totally produced at five open-air incineration sites, and consequently the formation amount of PCDDs, PCDFs and Co-PCBs was estimated to be 70.7 gTEQ on the basis of these analytical data.


Development of an amplified nanostructured electrochemical sensor for the detection of cefixime in pharmaceuticals and biological samples.
As one of the third generation of cephalosporin category, cefixime has a considerable activity towards both gram-positive and gram-negative bacteria so the quantitative analysis is considerable. Based on the synthesized reduced graphene oxide/CoFe2O4/ionic liquid (IL) (1-Ethyl-3-Methylimidazolium) (IL/CoFe2O4/rGO) nanocomposite, a modified carbon paste electrode (CPE) was selected as a sensor for determining cefixime. The structure and ability of nanostructures are investigated by various techniques containing scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), differential pulse voltammetry (DPV), cyclic voltammetry (CV) and chronoamperometry (CHA). The suggested sensor was successfully used for the simultaneous determination of cefixime, mefenamic acid, and acetaminophen. Under optimized settings, the oxidation peak current was obtained in the two linear ranges from 0.06 to 10 μM (0.02-4.53 µg.ml-1) (R2 = 0.9909) and 10.0-700.0 µM (4.53-317.394 µg.ml-1) (R2 = 0.9970) along with the detection limit of cefixime 0.035 μM (0.015 µg.ml-1). The values of electro-transfer coefficient (α) and diffusion coefficient (D) were achieved 0.9 and 1.17 × 10-6 cm2s-1. The electro-oxidation of cefixime occurs at an approximate potential of 0.85 V with an irreversible oxidation peak. The F-test (precision) and t-test (accuracy) were used for comparing the obtained results in urine samples. The proposed modified electrode shows high performance for the analysis of cefixime, mefenamic acid, and acetaminophen in pharmaceuticals and biological samples with good results.


Assessment of left ventricular performance by on-line pressure-area relations using echocardiographic automated border detection.
The purpose of this study was to evaluate left ventricular performance by on-line pressure-area relations using echocardiographic automated border detection in the in situ canine heart in a manner similar to pressure-volume analyses. Echocardiographic automated border detection can measure ventricular cavity area as an index of volume and may be interfaced with pressure to construct pressure-area loops on-line. Eight anesthetized open chest dogs had simultaneous measurement of ventricular pressure, aortic flow and midventricular short-axis area. Pressure-area loops were constructed by a computer workstation interfaced with the ultrasound system. Stroke area (Maximal area--Minimal area) and stroke force (integral of P dA [P = pressure; A = area]) values during inferior vena cava (n = 8) and aortic (n = 4) occlusions were compared with stroke volume and estimates of stroke work, respectively. Inotropic modulation was induced with dobutamine infusion (2 to 5 micrograms/kg body weight per min), followed by propranolol infusion (2 to 5 mg). End-systolic and maximal elastance and preload recruitable stroke force (stroke force versus end-diastolic area) were derived for each period. Changes in stroke area and stroke force were significantly correlated with changes in stroke volume and estimates of stroke work during caval occlusion (n = 8) (r = 0.87 +/- 0.02, SEE = 8 +/- 1% and r = 0.90 +/- 0.03, SEE = 8 +/- 2%, respectively). In dogs with aortic occlusion (n = 4), changes in stroke area significantly correlated with changes in stroke volume for pooled data (r = 0.84, SEE = 8%, y = 1.0x + 3). Ventricular performance increased with dobutamine infusion (n = 7): end-systolic elastance 30 +/- 11 to 67 +/- 24 mm Hg/cm2 (p < 0.02 vs. control values); maximal elastance 37 +/- 11 to 82 +/- 26 mm Hg/cm2 (p < 0.02 vs. control values); preload recruitable stroke force 81 +/- 24 to 197 +/- 92 mm Hg (p < 0.02 vs. control values). Decreases occurred with propranolol infusion (n = 5) end-systolic elastance 20 +/- 4 to 13 +/- 4 mm Hg/cm2 (p < 0.002 vs. control values); maximal elastance 29 +/- 8 to 15 +/- 5 mm Hg/cm2 (p < 0.002 vs. control values); preload recruitable stroke force 66 +/- 14 to 40 +/- 9 mm Hg (p < 0.002 vs. control values). On-line pressure-area relations are a potentially useful means to assess left ventricular performance in a manner that is quantitatively similar to the predicted responses of pressure-volume relations.


Microbiology of perianal cellulitis in children: comparison of skin swabs and needle aspiration.
To establish the aerobic and anaerobic microbiology of perianal cellulitis in children, comparing skin swab and needle aspirate methodology. Swabs of involved skin and needle aspirates of cellulitis were studied for aerobic and anaerobic bacteria. Specimens obtained from 10 patients with perianal cellulitis showed bacterial growth. Polymicrobial aerobic-anaerobic flora was found in all skin surface cultures, where the predominate isolates were Peptostreptococcus spp., Escherichia coli, and alpha hemolytic streptococci. The number of isolates in needle aspirates varied between one and two. The predominant ones were E. coli (3), Peptostreptococcus spp. (3), Staphylococcus aureus (2), and Bacteroides fragilis group (2). Complete or partial concordance in microbiology between skin swabs and needle aspirates was present in six instances. In four instances, isolates recovered from needle aspirates were not isolated from the skin surface. This study demonstrates the diversity of aerobic and anaerobic organisms isolated from perianal cellulitis, and the superiority of needle aspirates in establishing the microbiology of the infection.


Determination of metformin in human plasma by high-performance liquid chromatography.
A simple, selective and sensitive high-performance liquid chromatographic method with spectrophotometric detection was developed for the determination of antihyperglycemic agent metformin in human plasma using a novel sample extraction procedure. Liquid-liquid extraction of metformin and ranitidine (as internal standard) from plasma samples was performed with 1-butanol/n-hexane (50:50, v/v) in alkaline condition followed by back-extraction into diluted acetic acid. Chromatography was carried out using a silica column (250 mmx4.6 mm, 5 microm) under isocratic elution with acetonitrile-40 mM aqueous sodium dihydrogen phosphate (25:75, v/v), pH 6. The limit of quantification (LOQ) was 15.6 ng/ml and the calibration curves were linear up to 2000 ng/ml. The mean absolute recoveries for metformin and internal standard using the present extraction procedure were 98 and 95%, respectively. The intra- and inter-day coefficient of variation and percent error values of the assay method were all less than 8.3%.


Selective Immobilization of His-Tagged Phosphomannose Isomerase on Ni Chelated Nanoparticles with Good Reusability and Activity.
Self-stable precipitation polymerization was used to prepare an enzyme-immobilized microsphere composite. Phosphomannose isomerase (PMI) with His-tag was successfully immobilized on Ni2+ charged pyridine-derived particles. The maximum amount of PMI immobilized on such particles was ∼184 mg/g. Compared with free enzyme, the activity of the immobilized enzymes was significantly improved. In addition, the immobilized enzymes showed a much better thermostability than free enzymes. At the same time, the immobilized enzymes can be reused for multiple reaction cycles. We observed that the enzyme activity did not decrease significantly after six cycles. We conclude that the pyridine-derived particles can be used to selectively immobilize His-tagged enzymes, which can couple the enzyme purification and catalysis steps and improve the efficiency of enzyme-catalyzed industrial processes.


Dichotomous Role of Jasmonic Acid in Modulating Sorghum Defense Against Aphids.
The precursors and derivatives of jasmonic acid (JA) contribute to plant protective immunity to insect attack. However, the role of JA in sorghum (Sorghum bicolor) defense against sugarcane aphid (SCA) (Melanaphis sacchari), which is considered a major threat to sorghum production, remains elusive. Sorghum SC265, previously identified as a SCA-resistant genotype among the sorghum nested association mapping founder lines, transiently increased JA at early stages of aphid feeding and deterred aphid settling. Monitoring of aphid feeding behavior using electropenetrography, a technique to unveil feeding process of piercing-sucking insects, revealed that SC265 plants restricted SCA feeding from the phloem sap. However, exogenous application of JA attenuated the resistant phenotype and promoted improved aphid feeding and colonization on SC265 plants. This was further confirmed with sorghum JA-deficient plants, in which JA deficiency promoted aphid settling, however, it also reduced aphid feeding from the phloem sap and curtailed SCA population. Exogenous application of JA caused enhanced feeding and aphid proliferation on JA-deficient plants, suggesting that JA promotes aphid growth and development. SCA feeding on JA-deficient plants altered the sugar metabolism and enhanced the levels of fructose and trehalose compared with wild-type plants. Furthermore, aphid artificial diet containing fructose and trehalose curtailed aphid growth and reproduction. Our findings underscore a previously unknown dichotomous role of JA, which may have opposing effects by deterring aphid settling during the early stage and enhancing aphid proliferative capacity during later stages of aphid colonization on sorghum plants. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Trapping of arsenite by mercaptopropyl-functionalized mesostructured silica with a wormhole framework.
Thiol-functionalized mesostructured silica, prepared by direct assembly methods, is an effective trapping agent for the removal of arsenite from water.


Ultraviolet radiation-induced lethality and repair of pyrimidine dimers in fish embryos.
Pimephales promelas (fathead minnow) embryos were used to show a correlation between induction of pyrimidine dimers in DNA and embryo death. Embryo killing was measured by a lack of heart-beat and blood circulation at 48 h post-ultraviolet radiation (UVR). When the embryos were exposed to various doses of UVR from a FS-40 sunlamp followed by exposure to photoreactivating light (PRL) (320-400 nm), the number of pyrimidine dimers decreased significantly. The photorepair of dimers was accompanied by a substantial increase in embryo survival. When embryo killing was examined as a function of the number of dimers present, dimers were identified as a major lesion involved in UVR-induced killing in these fish embryos. This in vivo study on photoreactivation treatment of fish embryos shows a direct association between UVR-induced pyrimidine dimers and embryo killing. In addition, when embryos were held in the dark for 9 h after UVR, 50% of the dimers were removed by excision repair.


Omega 3 has a beneficial effect on ischemia/reperfusion injury, but cannot reverse the effect of stressful forced exercise.
The beneficial effects of exercise in reducing the incidence of cardiovascular diseases are well known. Several studies have demonstrated that forced exercise (FE) could activate a stress response similar to a restrain stress. Previous studies suggest that heart protection to ischemic events would be improved by an omega 3 free fatty acid (omega3-FFA)-enriched diet. Here, we investigate the impact of stressful FE and an omega 3-FFA-enriched diet on cardiac tolerance to ischemic events over one month. Twenty-four Wistar rats were randomly assigned to one of the following protocols: 1) Sedentary (SED) animals who were regularly fed; 2) sedentary animals who were given 1ml/day of fish oil for one month; 3) FE+omega3-FFA rats who were given 1ml/day of fish oil and forced to run on a motorized wheel for 30min every day, both for one month; and 4) FE animals were forced to exercise as group 3 and fed with a regular diet. At the end of the treatments an isolated heart preparation was performed. After a 30min global ischemic event and 2h reperfusion, hearts of sedentary-omega3 animals recovered about 37% of left ventricular developed pressure, whereas FE, omega3+FE and CTRL-SED animals recovered only about 15%, 5% and 8% respectively. Similarly, heart infarct size was significantly lower in sedentary-omega3 animals compared to animals in the three other groups. Results indicate that one month of treatment with an omega3-FFA-enriched diet improves cardioprotection upon ischemic events, whereas FE leads to a reduced heart tolerance to ischemic events, which cannot be reversed by an omega3-FFA diet.


Treatment decision-making strategies and influences in patients with localized prostate carcinoma.
Patients diagnosed with localized prostate carcinoma need to interpret complicated medical information to make an informed treatment selection from among treatments that have comparable efficacy but differing side effects. The authors reported initial results for treatment decision-making strategies among men receiving definitive treatment for localized prostate carcinoma. One hundred nineteen men treated with radical prostatectomy (44%) or brachytherapy (56%) consented to participate. Guided by a cognitive-affective theoretic framework, the authors assessed differences in decision-making strategies, and treatment and disease-relevant beliefs and affects, in addition to demographic and clinical variables. Approximately half of patients reported difficulty (49%) and distress (45%) while making treatment decisions, but no regrets (74%) regarding the treatment choice they made. Patients who underwent prostatectomy were younger, were more likely to be employed, had worse tumor grade, and had a shorter time since diagnosis (P < 0.01) compared with patients who did not undergo prostatectomy. In multivariate analyses, compared with patients who received radical prostatectomy, patients who received brachytherapy were more likely to say that they chose this treatment because it was "the least invasive" and they "wanted to avoid surgery" (P < 0.0001). In general, patients who received brachytherapy chose this treatment because of quality of life considerations, whereas "cure" and complete removal of the tumor were the main motivations for patients selecting radical prostatectomy. Long-term data are needed to evaluate distress and decisional regret as patients experience treatment-related chronic side effects and efficacy outcomes. Decision-making aids or other interventions to reduce decisional difficulty and emotional distress during decision making were indicated.


[Social inequality and health: Status and prospects of socio-epidemiological research in Germany].
Social differences in morbidity and mortality have always been a central topic in public health research. In recent years, there has been a growing research interest that has clearly resonated with the general public and the political arena as well. This article describes the development and establishment of social epidemiology in Germany and presents the current status of research. In addition, it describes different models for explaining health inequalities. On this basis, selected challenges and prospects of socio-epidemiological research are demonstrated. The reason why the analysis of social differences in morbidity and mortality will continue to be a key task of public health research in the national and international context in the future is also explained.


Customized prediction models based on APACHE II and SAPS II scores in patients with prolonged length of stay in the ICU.
To study customized APACHE II and SAPS II models in predicting hospital death in patients with a prolonged length of stay in the ICU. Prospectively collected database. Thirteen ICUs with 5-10 beds in Finnish secondary referral hospitals. None. The database was collected between 1994 and 1999 and included 23,953 ICU admissions. In order to customize the original APACHE II and SAPS II models and to validate the models, the database was randomly divided into customization data ( n=12,064) and into validation data ( n=11,889). Logistic regression analysis was used for customization. As the length of the ICU stay was prolonged, the calibration and discrimination of both customized models worsened gradually in the validation data. Patients whose ICU stay lasted 7 days or longer (1,312 patients) consumed more than one half of all ICU days and TISS-points. Among these patients, goodness-of-fit statistics was 221.5 and 306.3 ( P<0.0001 for both) and the areas under ROC curve 0.65 and 0.62 for the customized APACHE and SAPS models, respectively. The models underestimated the risk of death in the low range and overestimated it in the high range of predicted mortality. On the other hand, both models discriminated well between survivors and non-survivors if the ICU stay was 2 days or less. Despite customization, the predictive models may not support clinical decision-making in those patients who require a high share of resources. More relevant instruments are needed for the prediction of outcome of patient groups who consume the major part of ICU resources.


Methods of detection of mesenchymal stem cells in the kidneys during therapy of experimental renal pathologies.
We studied the possibility of using different methods for identification of mesenchymal multipotent stromal cells in the renal parenchyma under conditions of experimental thermal ischemia of the kidneys and acute pyelonephritis. In vivo and in vitro methods of identification of mesenchymal multipotent stromal cells by magnetic resonance imaging and immunological and immunohistochemical methods were compared. Labeling of stem cells with iron-containing particles followed by their histological identification and immunohistochemical staining with species-specific antibodies were the most informative methods. Active migration of the cells to the renal tissue was detected by these methods in experimental acute pyelonephritis with inflammation foci.


Percutaneous transcatheter embolization for arterial trauma.
With increasing technologic advances in interventional radiology, the vascular surgeon should be well versed in the indications, limitations, complications, and results of percutaneous transcatheter embolization for arterial trauma. Three hundred twenty-eight angiographically determined arterial injuries occurred in 242 patients from 1977 to 1984 in a major city hospital trauma center and were studied prospectively. Transcatheter embolizations performed for 107 arterial injuries in 100 patients were successful in 82.2% of injuries. Gelfoam, minicoils, microcoils, intimal dissections, or a combination of modalities was utilized. Anterior and posterior element pelvic fractures associated with hypotension and transfusion of 6 units or more of blood required embolization in 28 patients. Bleeding was controlled in 85.7% of patients. Percutaneous transcatheter embolization was also effective in controlling 84.2% of arteriovenous fistulas, 88.9% of penetrating neck arterial injuries, and 73.3% of postoperative intra-abdominal hemorrhage. Therapeutic transcatheter embolization is a valuable adjunct to the vascular surgeon dealing with the spectrum of vascular trauma.


Hemoglobin in Frankia, a nitrogen-fixing actinomycete.
Frankia strain CcI3 grown in culture produced a hemoglobin which had optical absorption bands typical of a hemoglobin and a molecular mass of 14.1 kDa. Its equilibrium oxygen binding constant was 274 nM, the oxygen dissociation rate constant was 56 s(-1), and the oxygen association rate constant was 206 microM(-1) s(-1).


A galactose polyacrylate-based hydrogel scaffold for the detection of cholera toxin and staphylococcal enterotoxin B in a sandwich immunoassay format.
A galactoside-based polyacrylate hydrogel was used as a scaffold to immobilize antibodies for the development of a sandwich immunoassay to detect cholera toxin (CT) and staphylococcal enterotoxin B (SEB). The hydrogel possesses large pores and simulates a solution-like environment allowing easy penetration of large biomolecules. Highly crosslinked hydrogels containing pendant amine or carboxyl functionalities were polymerized through a free-radical polymerization process. Covalent crosslinking of the antibodies on hydrogel films was accomplished using a homobifunctional crosslinker or carbodiimide chemistry. Utilizing the two different crosslinking methodologies, our results demonstrated the effectiveness of repetitive additions of crosslinker reactant into a single location on the gel surface. This approach in fact increased the amount of immobilized antibody. Patterned arrays of the immobilized antibodies for sandwich immunoassay development were achieved using a PDMS template containing micro-channels. This template provided a suitable means for applying reagents in multiple cycles. Fluorescence and three-dimensional (3D) imaging by confocal microscopy and laser scanning confocal microscopy of Cy3-labeled anti-CT and/or Cy3-anti-SEB tracer molecules provided qualitative and quantitative measurements on the efficiency of protein immobilization, detection sensitivity and signal-to-noise ratios. As a result of using the galactose polyacrylate-base hydrogel as a platform for immunoassay development, we have successfully been able to achieve low limits of detection for SEB and cholera toxins (1.0 ng mL(-1)). Repetitive additions (>3 cycles) of the crosslinker and antibody have also shown a dramatic increase in the immobilization of antibody resulting in improved immunoassay sensitivity. Fluorescence signal-to-noise ratios using the hydrogel-based immunoassays have been observed as high a 40:1.


Assessment of calf volume in Congenital Talipes Equinovarus by computer analysed digital photography.
The development of evidence-based approaches to the Congenital Talipes Equinovarus (CTEV) is impaired by the diversity of assessment techniques available, many of which have not been validated. Highly objective evaluation techniques that reflect the deformity and permit comparison between studies may lack the necessary link to functional features that are paramount to the patient, namely pain and mobility. Calf wasting is an acknowledged but little investigated component of the pathology. The rapid evolution of digital photography and computerised analytical techniques has yielded an opportunity to explore their role in the assessment of this common paediatric Orthopaedic pathology. This study presents the use of a cost-effective digital photographic assessment technique of maximal calf circumference and calf volume. These indices reflect the muscular development in the calf and therefore have significance in the functional assessment of CTEV and may represent an index of severity. Subjectivity has been limited by computerisation of the analysis process. The technique could easily be adapted to other volumetric analyses.


Oleanolic acid increases plasma ANP levels via an accentuation of cardiac ANP synthesis and secretion in rats.
Oleanolic acid is known to have beneficial effects on the regulation of cardiovascular homeostasis. The present study was designed to identify the effects of oleanolic acid on plasma levels and atrial synthesis and secretion of atrial natriuretic peptide (ANP). Experiments were performed in rats and isolated perfused beating rat atria. ANP was measured using a selective radioimmunoassay. ANP mRNA expression was measured using real-time quantitative polymerase chain reaction. Administration of oleanolic acid increased plasma ANP levels in a dose-related manner. Similarly, oleanolic acid increased atrial ANP content and ANP mRNA expression. To evaluate the effects of oleanolic acid on ANP secretion, atrial stretch and muscarinic acetylcholine receptor activation were applied to the atria from rats chronically treated with oleanolic acid. Baseline levels of ANP secretion were higher in the atria from rats treated with oleanolic acid compared to rats treated with vehicle. Furthermore, oleanolic acid treatment enhanced the stretch-induced increase in ANP secretion. Acetylcholine in the presence of isoproterenol increased ANP secretion. The acetylcholine-induced increase in ANP secretion was also enhanced in the atria from rats treated with oleanolic acid compared to atria from rats treated with vehicle. The present findings indicate that oleanolic acid increases plasma ANP levels via increased ANP synthesis and secretion in rats. It is proposed that an accentuation of the ANP system is involved in the beneficial effects of oleanolic acid on the regulation of cardiovascular homeostasis.


Species delimitation in a range-restricted group of cascudinhos (Loricariidae: Epactionotus) supports morphological and genetic differentiation across coastal rivers of southern Brazil.
Epactionotus species are known for inhabiting the rocky-bottom stretches of fast-flowing rivers in a limited geographic area along the Atlantic coast of southern Brazil. These species are endemic to single coastal river drainages (two neighbouring drainages for Epactionotus bilineatus) isolated from each other by the coastal lacustrine environments or the Atlantic Ocean. E. bilineatus is from the Maquiné and Três Forquilhas River basins, both tributaries of the Tramandaí River system, whereas E. itaimbezinho is endemic to the Mampituba River drainage and Epactionotus gracilis to the Araranguá River drainage. Recent fieldwork in the Atlantic coastal drainages of southern Brazil revealed new populations in the Urussanga, Tubarão, d'Una and Biguaçu River drainages. Iterative species delimitation using molecular data (cytochrome c oxidase subunit I) and morphology (morphometrics and meristics) was applied to evaluate species recognition of isolated populations. With regard to new data, the genus was re-diagnosed, the status of Epactionotus species/populations was re-evaluated, formerly described species were supported and population structure was recognized. As for the newly discovered populations, both morphological and molecular data strongly support the population from the Biguaçu River drainage, in Santa Catarina State, as a new species. Molecular data revealed strong per-basin population structure, which may be related to species habitat specificity and low or no dispersal among drainages.


Implementing Patient and Family Involvement Interventions for Promoting Patient Safety: A Systematic Review and Meta-Analysis.
The aims of the study were to evaluate and to quantify the effects of patient and family involvement (PFI) interventions on patient safety by synthesizing the available global data. Four databases were searched to identify relevant studies that have assessed the impact of PFI on patient safety up to March 2019. Reference lists of potential selected articles were also used to identify additional relevant studies. Effect sizes (ESs) were calculated using random and fixed effects models. Statistical heterogeneity was measured using the I2 test. Twenty-two studies met the review criteria. The meta-analysis showed that PFI were beneficial in significantly reducing adverse events (ES = -0.240, P < 0.001), decreasing the length of hospital stay (ES = -0.122, P < 0.001), increasing patient safety experiences (ES = 0.630, P = 0.007), and improving patient satisfaction (ES = 0.268, P = 0.004). However, the PFI interventions did not significantly enhance the perception of patient safety (ES = 0.205, P = 0.09) or the quality of life (ES = 0.057, P = 0.61). Moreover, moderate-to-high heterogeneity was found for all impacts except adverse events (I2 = 0%) and length of hospital stay (I2 = 35%). A funnel plot indicated a low degree of publication bias for the adverse event outcome. The synthesized evidence in this review demonstrates the benefits of PFI for promoting patient safety. However, further studies should extend the research scope to fill the existing gaps for both the type of PFI interventions and the patient safety outcomes.


Hippocampal atrophy and cognitive function in transient ischemic attack and minor stroke patients over three years.
Transient ischemic attack (TIA) and minor ischemic stroke (IS) is associated with a increased risk of late life dementia. In this study we aim to study the extent to which the rates of hippocampal atrophy in TIA/IS differ from healthy controls, and how they are correlated to neuropsychological measurements. TIA or minor stroke patients were tested with a neuropsychological battery including tests of executive function, and verbal and non-verbal memory at three time points out to 3 years. Annualized rates of hippocampal atrophy in TIA/IS patients were compared to controls. A linear-mixed regression model was used to assess the difference in rates of hippocampal atrophy after adjusting for time and demographic characteristics. TIA/IS patients demonstrated a higher hippocampal atrophy rate than healthy controls over a 3-year interval: the annual percentage change of the left hippocampal volume was 2.5% (78 mm3 per year (SD 60)) for TIA/IS patients compared to 0.9% (29 mm3 per year (SD 32)) for controls (p < 0.01); and the annual percentage change of the right hippocampal volume was 2.5% (80 mm3 per year (SD 46)) for TIA/IS patients compared to 0.5% (17 mm3 per year (SD 33)) for controls (P < 0.01). Patients with higher annual hippocampal atrophy were more likely to report higher TMT B times, but lower ROC total score, lower California Verbal Learning Test-II total recall, and lower ROC Figure recall scores longitudinally. TIA/IS patients experience a higher rate of hippocampal atrophy independent of TIA/IS recurrence that are associated with changes in episodic memory and executive function over 3 years.


Functional Cardiovascular Characterization of the Common Marmoset (Callithrix jacchus).
Appropriate cardiovascular animal models are urgently needed to investigate genetic, molecular, and therapeutic approaches, yet the translation of results from the currently used species is difficult due to their genetic distance as well as their anatomical or physiological differences. Animal species that are closer to the human situation might help to bridge this translational gap. The common marmoset (Callithrix jacchus) is an interesting candidate to investigate certain heart diseases and cardiovascular comorbidities, yet a basic functional characterization of its hemodynamic system is still missing. Therefore, cardiac functional analyses were performed by utilizing the invasive intracardiac pressure-volume loops (PV loop) system in seven animals, magnetic resonance imaging (MRI) in six animals, and echocardiography in five young adult male common marmosets. For a direct comparison between the three methods, only data from animals for which all three datasets could be acquired were selected. All three modalities were suitable for characterizing cardiac function, though with some systemic variations. In addition, vena cava occlusions were performed to investigate the load-independent parameters collected with the PV loop system, which allowed for a deeper analysis of the cardiac function and for a more sensitive detection of the alterations in a disease state, such as heart failure or certain cardiovascular comorbidities.


The contractile apparatus of striated muscle in the course of atrophy and regeneration. II. Myosin and actin filaments in mature rat soleus muscle regenerating after reinnervation.
Changes in the contractile apparatus of denervated rat soleus muscles were investigated during the course of reinnervation. As observed earlier, in the course of denervation atrophy the ratio of myosin to actin filaments decreases because myosin filaments disappear faster than actin filaments (Jakubiec-Puka et al. 1981 a). After reinnervation the amount of myosin filaments and myosin heavy chains (myosin HC) in the muscle increased during the first few days; the increment of actin content was negligible. The proportion of myosin HC to actin remained lower than normal for about 30 days. The excess of actin filaments frequently observed in the newly-formed myofibrils reflects this disproportion. The results show a lability of myosin and suggest some cytoskeletal role for actin filaments.


Superficial Acral Fibromyxoma: Literature Review.
Superficial acral fibromyxoma is a benign and rare tumor of the soft tissues. It usually manifests itself through a painless mass of slow growth that affects mainly males in the fifth decade of life. It usually affects the distal region, with a polypoid or dome-shaped appearance. The histological appearance is of a dermal mass without capsule, with spindle-shaped fibroblasts in a storiform or fasciculated pattern in the myxocollagenous stroma. The immunohistochemical evaluation of superficial acral fibromyxoma is usually positive for CD34 and CD99, with variable positivity for epithelial membrane antigen. The treatment consists of complete excision of the tumor mass. A review of the current literature on superficial acral fibromyxoma was performed, with an emphasis on the number of cases reported, location, diagnostic methods, histological characteristics, differential diagnoses and treatment. A total of 314 reported cases of superficial acral fibromyxoma with variable locations were found in the current literature, mainly in the toes (45.8%) and fingers (39.1%). It has a slightly superior incidence in men (61%) and enormous variability in the age range of occurrence. Superficial acral fibromyxoma is a single soft-tissue tumor that should enter the differential diagnosis of periungual and subungual acral lesions; the treatment consists of simple excision. More studies are needed to better understand this pathology, which was first described in 2001.


Modulation of tumor necrosis factor-alpha and oxidative stress through protein kinase C and P42/44 mitogen-activated protein kinase in lead increases lipopolysaccharide-induced liver damage in rats.
Lead (Pb) increases lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), lipid peroxidation (LPO), and liver damage. In this study, we investigated the role of protein kinase C (PKC) and p42/44 mitogen-activated protein kinase (MAPK) and the causal relationships between TNF-alpha, NO, and LPO in Pb-increased LPS-induced liver damage in rats. Treatment with PKC and p42/44 MAPK inhibitors significantly reduced Pb + LPS-induced NO, TNF-alpha, LPO, and liver damage, which was revealed by elevated serum levels of aspartate aminotransferase and alanine aminotransferase. Pb + LPS coexposure significantly increased phosphorylation of p42/44 MAPK and TNF-alpha expression in peripheral blood cells; however, exposure to Pb + LPS did not induce TNF-alpha, NO, or LPO production and p42/44 MAPK activation in the liver. Pentoxifylline, a TNF-alpha inhibitor, also reduced liver damage but did not alter NO or LPO in Pb + LPS-treated rats. Thus, Pb increased LPS-induced liver damage through PKC and p42/44 MAPK modulation of TNF-alpha and oxidative stress, but modulation of TNF-alpha did not affect NO or LPO in rats.


Primary cerebral venous thrombosis in young adults: the diverse manifestations of an underrecognized disease.
Primary cerebral venous thrombosis has a wide clinical and pathological spectrum, which has not been recognized. Seven cases of aseptic cerebral venous thrombosis (5 fatal) are discussed, with pathological study and literature review. Five patients ranged in age from 22 to 31 years. In 3 cases no discernible cause for thrombosis was found. Novel features of these cases include: primary bilateral internal cerebral venous thrombosis; isolated thrombocytopenia; occurrence in the context of (1) ulcerative colitis plus oral contraceptive use, (2) a twin transfusion syndrome, and (3) presenting syndrome five years after mastectomy for carcinoma. Diagnosis and treatment are discussed, and it is suggested that a focal coagulopathy may be responsible for this underdiagnosed condition.


Atrial natriuretic peptide serum concentration decreases in donors undergoing discontinuous plasmapheresis involving a large extracorporeal blood volume.
In donor plasmapheresis, circulatory reactions occur at a similar frequency as in whole-blood donation although the large extracorporeal blood volume (ECV) occurring during discontinuous plasmapheresis might predispose donors to hypovolemic reactions. The regulatory mechanisms compensating for this intradonation blood volume (BV) deficit are not well understood. It was the aim of this study to delineate whether atrial natriuretic peptide (ANP) is involved in the BV regulation of plasmapheresis donors. Because ANP regulates volume overload, it might decrease during BV decrease in plasmapheresis. ANP serum concentrations were determined in 60 donors undergoing discontinuous plasmapheresis. Samples were taken before the start of the procedure and when maximum ECV (ECV(max)) was reached at the end of the last withdrawal. Donors were randomly selected after stratification for sex and BV. In a control investigation, the same donors were kept in a reclined position for the duration of a plasmapheresis session without plasma withdrawal. ANP plasma concentration changes were correlated with changes of hemodynamic variables, which were recorded noninvasively with bioelectrical impedance cardiography. Median ANP concentration decreased from 13.0 to 8.4 pg per mL during donation and from 11.6 to 10.5 pg per mL during the control session. The mean control-adjusted ANP change due to plasma withdrawal was -2.62 pg per mL (p = 0.006). This decrease was not attributable to a dilution effect. ANP change did not correlate with changes of recorded hemodynamic variables. The decrease of the ANP serum concentration during plasmapheresis demonstrates that the ECV(max) constitutes a hypovolemic challenge of the donors, which elicits a neurohormonal regulatory mechanism aimed at maintaining cardiovascular homeostasis.


Outcome of complete acellular dermal matrix wrap with polyurethane implant in immediate prepectoral breast reconstruction.
Polyurethane implants have been used on and off in breast reconstruction since 1991 while prepectoral breast reconstruction has gained popularity in recent times. In this study, we present our outcomes from the use of acellular dermal matrix (ADM) complete wrap with polyurethane implants in prepectoral breast reconstruction. This is a retrospective review of prospectively maintained database from 41 patients receiving complete ADM wrap with prepectoral polyurethane implants over a 3-year period. Selection criteria were adapted from a previous study (4135 Trust Clinical Audit Database) evaluating prepectoral reconstruction with Braxon matrices. Patient demographics, operative data, surgical complications, and outcomes were collected and analyzed. A total of 52 implant reconstructions were performed in 41 patients with a mean follow-up of 14.3 months (range, 6-36 months). The overall reported complication rates including early (less than 6 weeks) and late complications. Early complications included two patients (4.9%) with wound dehiscence. One of which had an implant loss that was salvageable. Another patient (2%) developed red-breast syndrome and two women (4.9%) developed with seroma treated conservatively. Late complications included one patient (2%) with grade II capsular contraction, 12 patients with grade I-II rippling and two patients (4.9%) with grade III rippling. We present our experience of prepectoral polyurethane implant using complete ADM wrap. This is one of the few papers to report on the outcome of the prepectoral use of polyurethane in immediate implant-based breast reconstruction. Our early observational series show satisfactory outcome and long-term results are warranted by a large multicenter study.


A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease.
To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH). MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors. Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated. Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH. Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS. Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.


Effect of pH and stimulus phase on work done by isolated frog sartorius muscle during cyclical contraction.
Work per cycle was calculated in isolated frog sartorius muscle by measuring force as the activated muscle was subjected to sinusoidal length changes. Work per cycle was calculated from the area of the loop formed when force was plotted against length. Measurements were made at 20 degrees C using physiological solutions with high pHe (7.9 or low pHe (6.6). Net work done per cycle was positive when the muscle was activated during the shortening phase of the length cycle. Maximum work done increased as excursion amplitude increased and was about 17Jkg-1 at a strain of 12% (i.e. Lo +/- 6%) at a cycle frequency of 2 Hz. Maximum power was 35 W kg-1 and was about 25% less at the lower pHe. Power measured in this way is much less than the value calculated from force-velocity curves. However, power calculated from force-velocity curves neglects the time that the muscle must be inactive during locomotion. Thus the measurements of the present study are realistic relative to actual mechanical power output during locomotion.


Updates in heart transplantation.
Heart transplantation (HTx) has been a successful therapy for patients with end-stage heart failure. Since 1987, we have performed 288 HTx. Thirty-six subjects needed mechanical support prior to HTx. We use anti-thymocyte globulin (ATG) as induction therapy and low-dose immunosuppressive agents for maintenance treatment. In June 1996, we performed combined heart and kidney transplantation after bridging for 14 days with an indigenous total artificial heart (TAH). The patient is still well. Our actuarial survival rates at 1, 5, and 10 years are 86%, 76%, and 61%, respectively. One recipient who voluntarily discontinued all treatment at 4 years after HTx is still alive and free of rejection in his ninth posttransplantation year. The longest surviving recipient is in her 18th posttransplantation year. We also have used many suboptimal donor hearts, most with satisfactory outcomes. A 14-year-old boy had full recovery of heart function after receiving a donor heart after 13 hours of ischemia in 2003. Standard biatrial anastomotic technique is still our first choice. The incidence of tricuspid regurgitation (TR) and conduction disturbances is not higher than the bicaval technique reported by others. With low-dose therapy, our short-term and long-term results of HTx are satisfactory. The use of suboptimal donor hearts may expand the donor pool and save more patients' lives. A biatrial anastomosis remains our surgical technique.


Current concepts on physiological control of gastric acid secretion. Clinical applications.
Gastric acid secretion by the parietal cell is a single digestive process involving a continuous interplay between nervous and hormonal stimuli. Gastric acid hypersecretion and hypergastrinemia may represent pathologic disturbance of the normal "gastric phase" of acid secretion (excluded antrum syndrome) or abnormal gastrin secretion from a nongastric source as in the Zollinger-Ellison syndrome. Diagnosis of these two syndromes preoperatively is dependent on immunoassay for serum gastrin. A fall in serum gastrin level after the injection of secretin will distinguish the excluded antrum syndrome from the Zollinger-Ellison syndrome. Which hormone or hormones cause the acid hyposecretion of the watery diarrhea hypokalemia achlorhydria syndrome is still uncertain. Potential candidates include secretin, glucagon (alone or combined with gastrin), vasoactive intestinal peptide and gastric inhibitory polypeptide. Secretin has undergone trials as therapy in peptic ulcer whereas glucagon is under investigation for the treatment of acute pancreatitis because of its dual actions as (1) an enterogastrone and (2) an inhibitor of pancreatic secretion.


[Experimental and histomorphologic studies of healing processes of anastomoses of the carotid artery in the Wistar rat animal model with immunohistochemical imaging of collagen IV].
The main risk in free flap tissue transfer is posed by the microvascular anastomosis. The dangers confronting the anastomosis are thrombosis, aneurysm, and vascular insufficiency. Collagen IV is associated with the basement membrane complex. It plays an essential role in vascular tissue organization and supports mechanical properties of vessels. We used a long-term animal experiment to gain a new understanding of histomorphological apposition of anastomosis and distribution of collagen IV. Seventy Wistar rats, seven groups of ten animals each, were operated. A 4-mm long segment of the common carotid artery was isolated and reinserted. After a varying length of time (between directly after the operation and 6 months later), the common carotid arteries including bifurcation were isolated after cardiovascular perfusion. Carotid arteries were embedded, and cross-sections were stained with hematoxylin and eosin, Verhoeff's tissue elastin stain, and immunohistochemical anti-collagen IV antibody. By using the above-described technique in each section four anastomoses were examined. The histomorphology and intensity of the anti-collagen IV stainings were evaluated. Compression, shift, and dehiscence as forms of vessel apposition were often seen. We observed an overexpression of collagen IV in the media in cases of compression and shift. The grade of expression of collagen IV in the anastomosis depends on the extent of the injury. A well-performed microvascular anastomosis is clinically important not only for the acute phase after the operation, but also for the long-term course. The application of antibodies to identify the collagen IV distribution is valuable for studying vascular healing. Further applications could be used in follow-up studies of vascular prostheses.


Targeting of the adaptor protein Tab2 as a novel approach to revert tamoxifen resistance in breast cancer cells.
Pharmacological resistance is a serious threat to the clinical success of hormone therapy for breast cancer. The antiproliferative response to antagonistic drugs such as tamoxifen (Tam) critically depends on the recruitment of NCoR/SMRT corepressors to estrogen receptor alpha (ERα) bound to estrogen target genes. Under certain circumstances, as demonstrated in the case of interleukin-1β (IL-1β) treatment, the protein Tab2 interacts with ERα/NCoR and causes dismissal of NCoR from these genes, leading to loss of the antiproliferative response. In Tam-resistant (TamR) ER-positive breast cancer cells, we observed that Tab2 presents a shift in mobility on sodium dodecyl sulfate--PAGE (SDS-PAGE) similar to that seen in MCF7 wt upon stimulation with IL-1β, suggesting constitutive activation. Accordingly, TamR treatment with Tab2-specific short interfering RNA, restored the antiproliferative response to Tam in these cells. As Tab2 is known to directly interact with the N-terminal domain of ERα, we synthesized a peptide composed of a 14-aa motif of this domain, which effectively competes with ERα/Tab2 interaction in pull-down and co-immunoprecipitation experiments, fused to the carrier TAT peptide to allow internalization. Treatment of TamR cells with this peptide resulted in partial recovery of the antiproliferative response to Tam, suggesting a strategy to revert pharmacological resistance in breast cancer. Silencing of Tab2 in TamR cells by siRNA caused modulation of a gene set related to the control of cell cycle and extensively connected to BRCA1 in a functional network. These genes were able to discern two groups of patients, from a published data set of Tam-treated breast cancer profiles, with significantly different disease-free survival. Altogether, our data implicate Tab2 as a mediator of resistance to endocrine therapy and as a potential new target to reverse pharmacological resistance and potentiate antiestrogen action.


Dissecting the structural and functional features of the Luteinizing hormone receptor using receptor specific single chain fragment variables.
The Luteinizing hormone receptor (LHR) has a large extracellular domain (amino acid residues, a.a.1-355) and a transmembrane domain (TMD; a.a. 356-699), essential for hormone binding and signaling, respectively. The LHR hinge region (a.a. 256-355) connects the two domains and acts as an activating switch for the receptor by an unknown mechanism. LHR hinge-specific Single chain fragment variables (ScFv) stimulated cAMP production by the stable and transiently transfected cell lines expressing LHR in a hormone-independent manner and the C-terminal region of LHR hinge (a.a. 313-349) was identified as the probable epitope for one agonistic ScFv. This epitope attained a helical conformation upon agonistic ScFv binding and the activity of the ScFv was dependent on Y331 sulfation. ScFv was also able to activate TMD mutants, D578Y and A593P, reemphasizing the role of TM helix VI in LHR activation.


Utility of Risk Stratification for Paclitaxel Hypersensitivity Reactions.
Hypersensitivity reactions (HSRs) are a common impediment to paclitaxel therapy. Management strategies to guide care after a paclitaxel-induced HSR are needed. The objective was to evaluate the utility and safety of risk stratification on the basis of severity of the initial HSR. A risk stratification pathway was developed on the basis of a retrospective review of the management and outcome of 130 patients with paclitaxel-induced HSRs at Massachusetts General Hospital. This pathway was then studied prospectively in patients referred to Allergy/Immunology with paclitaxel-induced HSRs. The study population (n = 35) had a mean age of 56.1 ± 12 years and most were women (n = 33 [94%]). All 5 patients (15%) with grade 1 initial HSRs were successfully reexposed to paclitaxel, 1 patient at the standard infusion rate and 4 patients at 50% of the standard infusion rate. Thirty patients (85%) with grade 2 to 4 initial HSRs underwent initial paclitaxel desensitization based on the risk stratification pathway. No patients developed severe HSRs using the pathway. Eleven (31%) patients had HSRs that were mild to moderate in nature (grade 1, n = 4 [11%]; grade 2, n = 6 [17%]; grade 3, n = 1 [3%]) during their first desensitization. Sixteen (46%) of the 35 patients safely returned to the outpatient infusion setting for paclitaxel treatment at 50% of the standard infusion rate. Seven (20%) discontinued paclitaxel before the completion of the risk stratification pathway because of disease progression, completion of therapy, or death. A management strategy using the initial HSR severity for risk stratification allowed patients to receive paclitaxel safely.


Identification of genetic variants and phenotypic characterization of a large cohort of patients with congenital hypopituitarism and related disorders.
Congenital hypopituitarism (CH) disorders are phenotypically variable. Variants in multiple genes are associated with these disorders, with variable penetrance and inheritance. We screened a large cohort (N = 1765) of patients with or at risk of CH using Sanger sequencing, selected according to phenotype, and conducted next-generation sequencing (NGS) in 51 families within our cohort. We report the clinical, hormonal, and neuroradiological phenotypes of patients with variants in known genes associated with CH. We identified variants in 178 patients: GH1/GHRHR (51 patients of 414 screened), PROP1 (17 of 253), POU1F1 (15 of 139), SOX2 (13 of 59), GLI2 (7 of 106), LHX3/LHX4 (8 of 110), HESX1 (8 of 724), SOX3 (9 of 354), OTX2 (5 of 59), SHH (2 of 64), and TCF7L1, KAL1, FGFR1, and FGF8 (2 of 585, respectively). NGS identified 26 novel variants in 35 patients (from 24 families). Magnetic resonance imaging showed prevalent hypothalamo-pituitary abnormalities, present in all patients with PROP1, GLI2, SOX3, HESX1, OTX2, LHX3, and LHX4 variants. Normal hypothalamo-pituitary anatomy was reported in 24 of 121, predominantly those with GH1, GHRHR, POU1F1, and SOX2 variants. We identified variants in 10% (178 of 1765) of our CH cohort. NGS has revolutionized variant identification, and careful phenotypic patient characterization has improved our understanding of CH. We have constructed a flow chart to guide genetic analysis in these patients, which will evolve upon novel gene discoveries.


Ventricular configuration and cerebral growth in infants born to drug-dependent mothers.
Cranial ultrasound examinations were performed during the first 3 days of life and at age 1 month on 22 infants with the neonatal abstinence syndrome. The results were compared to those obtained in 15 control infants who were not exposed to narcotic drugs in utero. The ultrasound images were examined for ventricular configuration, intracranial hemidiameters, area of thalami, and width of temporal lobes. At 24 to 72 h and at 1 month of age, significantly more drug-exposed than control infants had a slit-like ventricular configuration. The intracranial hemidiameter was significantly smaller in the drug-exposed than in the control infants. All cerebral measurements except the right temporal lobe demonstrated significant growth over the first month of life in both groups of infants. By means of ancillary examinations (computerized tomography and transfontanel pressure measurements) the pathogenesis of the slit-like ventricles was found not to be related to edema or to increased intracranial pressure. Whether or not the ventricles remain small and brain growth remains parallel after the period of abstinence awaits further investigation.


Data for the identification of proteins and post-translational modifications of proteins associated to histones H3 and H4 in S. cerevisiae, using tandem affinity purification coupled with mass spectrometry.
Tandem affinity purification method (TAP) allows the efficient purification of native protein complexes which incorporate a target protein fused with the TAP tag. Purified multiprotein complexes can then be subjected to diverse types of proteomic analyses. Here we describe the data acquired after applying the TAP strategy on histones H3 and H4 coupled with mass spectrometry to identify associated proteins and protein post-translational modifications in the budding yeast, Saccharomyces cerevisiae. The mass spectrometry dataset described here consists of 14 files generated from four different analyses in a 5600 Triple TOF (Sciex) by information-dependent acquisition (IDA) LC-MS/MS. The above files contain information about protein identification, protein relative abundance, and PTMs identification. The instrumental raw data from these files has been also uploaded to the ProteomeXchange Consortium via the PRIDE partner repository, with the dataset identifier PRIDE: PXD002671 and http://dx.doi.org/10.6019/PXD002671. These data are discussed and interpreted in http://dx.doi.org/10.1016/j.jprot.2016.01.004. Valero et al. (2016) [1].


Nitric oxide involvement and neural substrates of the conditioned and innate fear as evaluated in the T-maze test in rats.
The L-arginine/nitric oxide (NO) pathways are widely distributed in the central nervous system (CNS) and have been implicated in the modulation of anxiety. The elevated plus-maze (ETM) is an animal test pharmacologically validated for the study of experimental anxiety in rats, designed to evaluate inhibitory avoidance (AVOID) learning and one-way escape (ESC) from open arms, thought to represent learned (conditioned) and innate (unconditioned) fear, respectively. The aim of the present study was to evaluate the effect of prior treatment with the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on both AVOID and ESC behavior of rats in the ETM, when applied to different cerebral regions associated with defensive behaviors. Central treatment with L-NAME (50, 100, 400 and 800 nmol) did not impair the AVOID response through the trials and had no effect on the ESC behavior. Nevertheless, animals treated with L-NAME at 200 nmol into the lateral ventricle (LV), basolateral amygdala (BLA), dorsolateral periaqueductal gray (dlPAG) matter, lateral septal nucleus (LSN), but not in the bed nucleus of stria terminalis (BNST), displayed impaired AVOID2 in comparison to the control group. Thus, our results suggest that NO may underlie learned fear in the ETM via BLA, dlPAG and LSN, but not BNST. These results are compatible with the proposal that NO exerts a positive modulatory role on defensive reactions in rats, exerting among them an anxiogenic-like effect as evaluated in rats submitted to ETM.


Reducing the vermilion notch in primary lip repairs: Z-plasty versus the Noordhoff triangular flap.
To compare Z-plasty and the Noordhoff flap for reducing notching in the vermilion during primary repair. Comparative study. Plastic Surgery Department, Mayo Hospital, Lahore, from March 2008 to August 2010. Patients presenting for primary unilateral cleft lip repair were included. The modified Millard's technique was used for lip repair. The percentage of the total vermilion thickness notched was recorded at 6 months follow-up. The repair was graded as: < 0.5 mm good, > 0.5 mm but < 1 mm satisfactory and > 1 mm poor. Patient satisfaction was rated on a scale of 1 to 10, with 10 being the happiest patient. In Group 1 (Z-plasty) 25 patients, and in Group 2 (Noordhoff flap), 20 patients achieved a good result. Five patients in Group 1 and 7 patients in Group 2 achieved a satisfactory result. Three patients in Group 2 had a poor result. Patient satisfaction and vermilion repair were comparable when comparison was made between the two groups (p > 0.05). The Noordhoff flap needs more expertise and finesse. All 3 poor results were achieved early in the study. Z-plasty was easier to execute and gave a good result in almost all hands.


Inhibition of store-operated Ca2+ entry suppresses EGF-induced migration and eliminates extravasation from vasculature in nasopharyngeal carcinoma cell.
Store-operated Ca(2+) entry (SOCE) mediates Ca(2+) responses evoked by extracellular signaling molecules to promote increases in cytosolic Ca(2+), thereby triggering downstream signal transduction. Here we demonstrated that either the pharmacological blockage of Ca(2+) influx through SOCE or the knockdown of Orai1, a key molecule of SOCE, suppressed the epidermal growth factor-induced migration by disturbing Ca(2+) signaling in nasopharyngeal carcinoma (NPC) cell. Furthermore, Orai1 depletion led to a delayed cell attachment to the extracellular matrix surface in vitro and eliminated the extravasation of microinjected cells from vasculature in a zebrafish hematogenous metastasis model. Our findings thus indicate that SOCE acts as a predominant Ca(2+) signaling involved in NPC cell metastasis, and may serve as a candidate target for anti-metastasis therapy in NPC.


Possible down regulation of the p16 gene promoter in individuals with hepatocellular carcinoma.
The p16 tumor suppressor gene is an important negative regulator of the cell cycle. Inactivation of p16, especially via promoter hypermethylation, has been found in numerous human cancers such as breast, lung, colorectal, and liver. To determine the role of epigenetic methylation in p16 regulation in Iranian patients with hepatocellular carcinoma (HCC). The methylation pattern in the p16 gene promoter was analyzed by bisulfite direct sequencing in 43 paraffin-embedded formalin-fixed tissues from patients with HCC. In addition, normal specimens from liver graft donors were used as the control group. The bisulfite direct sequencing showed heterozygous hypermethylation in 13.9% of individuals with HCC. Homozygous methylation within the GC-box IV was detected in another 58.1% of the patients. It is proposed that methylation, but not necessarily hypermethylation, may play a role in the down-regulation of the p16 gene promoter at least in some Iranian patients with HCC.


Monolayer-graphene-based broadband and wide-angle perfect absorption structures in the near infrared.
Broadband optical absorption structures in the near infrared by coupling monolayer-graphene with periodical metal structures are proposed and demonstrated numerically. Optical absorption of graphene with over-50%-absorption bandwidth up to hundreds of nanometer caused by magnetic dipole resonances and magnetic coupling effect are investigated in detail, and the demonstrated bandwidths are one order higher than those caused by dielectric guiding mode resonances. In addition, the influences of geometrical parameters of structures are fully analyzed and these demonstrated structures show angular-insensitive absorption for oblique incidence in a large angular range. The demonstrated absorption structures in this work provide new design ideas in the realization of advanced graphene-based optoelectronic devices.


Isoprenaline-induced myocardial infarction in spontaneously hypertensive rats.
Spontaneously hypertensive rats were subjected to massive myocardial infarction. The pathophysiological changes were similar to those of normotensive rats but the spontaneously hypertensive rats developed congestive heart failure during myocardial repair rather than during the necrosis phase and survived in superior numbers. Blood pressure fell despite maximally increased corticosterone levels. Atrial and ventricular thromboses and left ventricular aneurysm formation were frequent.


The binding properties of the H5N1 influenza virus neuraminidase as inferred from molecular modeling.
The avian influenza H5N1 virus has emerged as an important pathogen, causing severe disease in humans and posing a pandemic threat. Substrate specificity is crucial for the virus to obtain the ability to spread from avian to human. Therefore, an investigation of the binding properties of ligands at the molecular level is important for understanding the catalytic mechanism of the avian influenza virus neuraminidase and for designing novel and specific inhibitors of H5N1 neuraminidase. Based on the available crystal structure of H5N1, we have characterized the binding properties between sialic acid, methyl 3'sialyllactoside, methyl 6'sialyllactoside and the H5N1 influenza virus neuraminidase using molecular docking and molecular dynamics simulations. Obtained molecular dynamics trajectories were analyzed in terms of ligand conformations, N1-ligand interactions, and in terms of loop flexibility. It was found that in the N1-SA complex the sialic acid ring undergoes a transition from the B(2,5) to the (2)C(5) conformation. However, in the N1-3SL and N1-6SL complexes sialic acid remained in the distorted boat conformation. The obtained results indicate that 3SL has only weak interactions with the 150-loop, whereas the N1-6SL complex shows strong interactions. Most of the differences arise from the various conformations around the glycosidic linkage, between the sialic acid and galactose, which facilitate the above interactions of 6SL with the enzyme, and as a consequence the interactions between the 150- and 430- loops. This finding suggests that the altered flexibility of loops in and around the active site is one of the reasons why the avian N1 preferentially cleaves sialic acid from α-(2-3)-Gal glycoconjugates over α-(2-6)-Gal. These molecular modeling results are consistent with available experimental results on the specificity of N1.


Adiponectin stimulates phosphorylation of AMP-activated protein kinase alpha in renal glomeruli.
Adiponectin receptor ADIPOR1 activates the intracellular second messenger AMP-activated protein kinase (AMPK) that participates in the control of the oxidative stress and apoptosis. This study reveals the presence of a functional ADIPOR1 receptor in all the cells of the renal glomeruli. Isolated glomeruli were incubated in vitro with adiponectin and proteins analysed by western blot. Electron microscopy using immunogold labeling was carried out on kidney sections. ADIPOR1 and catalytic AMPK sub-units alpha1 and alpha2 were revealed in normal rat glomeruli and incubation of freshly isolated rat glomeruli with either adiponectin or AICAR led to the activation by phosphorylation of catalytic AMPK. Electron microscopy localized with high resolution these proteins at the plasma membrane of the three glomerular cells, namely the endothelial, the mesangial and the podocyte cells, as well as on Bowman's capsule epithelial cells. It is concluded that glomerular cells express a functional adiponectin receptor ADIPOR1 which, through activation of AMPK, may play important roles in the control of oxidative stress and cell survival within the glomerulus.


Diminished pressor response to exogenous norepinephrine and angiotensin II in septic, unanesthetized rats: evidence for a prostaglandin-mediated effect.
Despite elevated plasma concentrations of norepinephrine (NE), septic patients generally have normal or low mean arterial pressure (MAP) and systemic vascular resistance. We tested the hypothesis that sustained sepsis in rats results in relative hyporesponsiveness to the pressor actions of NE and angiotensin II (AII). Sprague-Dawley rats were studied 48 hr after sepsis was induced by cecal ligation. Sham-operated rats served as controls. Carotid artery and jugular venous catheters were placed under halothane anesthesia and the rats were allowed to waken fully in restraining cages. Peak increments in MAP were measured after bolus iv doses of NE (0.125-8.0 micrograms/kg) or AII (0.0125-0.5 microgram/kg). Some rats were pretreated with indomethacin (5 mg/kg, iv) 30 min prior to the dose-response study. Data were fitted to a two-parameter hyperbolic function and the resulting curves were compared by analysis of variance. Compared with controls, sepsis decreased the pressor response to both NE (P less than 0.0001) and AII (P less than 0.0001). Indomethacin restored responsiveness toward normal for both pressor agents (P less than 0.0001). It is concluded that sepsis is associated with hyporesponsiveness to two chemically dissimilar vasopressors and that this phenomenon may be mediated by prostaglandins.


Global and regional estimates of orphans attributed to maternal cancer mortality in 2020.
Despite women being disproportionally affected by cancer deaths at young ages, there are no global estimates of the resulting maternal orphans, who experience health and education disadvantages throughout their lives. We estimated the number of children who became maternal orphans in 2020 due to their mother dying from cancer in that year, for 185 countries worldwide and by cause of cancer-related death. Female cancer deaths-by country, cancer type and age (derived from GLOBOCAN estimates)-were multiplied by each woman's estimated number of children under the age of 18 years at the time of her death (fertility data were derived from United Nations World Population Prospects for birth cohort), accounting for child mortality and parity-cancer risk associations. Globally, there were 1,047,000 such orphans. Over half of these were orphans due to maternal deaths from breast (258,000, 25%), cervix (210,000, 20%) and upper-gastrointestinal cancers (136,000, 13%), and most occurred in Asia (48%: India 15%, China 10%, rest of Asia 23%) and Africa (35%). Globally, there were 40 new maternal orphans due to cancer per 100,000 children, with a declining trend with a higher Human Development Index (range: 121 in Malawi to 15 in Malta). An estimated 7 million children were prevalent maternal orphans due to cancer in mid-2020. Accelerating the implementation of the World Health Organization's cervical and breast cancer initiatives has the potential to avert not only millions of preventable female cancer deaths but also the associated, often-overlooked, intergenerational consequences of these deaths.


Liver Stiffness is Reduced to Normal After Successful Renal Transplantation: A Prospective Cohort Study.
Liver stiffness (LS) may be falsely elevated in patients on maintenance hemodialysis (MHD) due to fluid overload. We measured LS change by transient elastography (TE) in MHD patients before and after successful renal transplantation. Adults on ≥2 years of MHD, without additional risk factors for liver fibrosis or fluid overload, and planned for renal transplantation were prospectively recruited. LS was measured on two occasions, i.e., within two weeks before transplantation (pre-Tx LS) and after ≥ 3 months after successful transplantation (post-Tx LS). The participants with pre-Tx LS ≤ 7.0 KPa and >7.0 KPa were classified as "Group I" and "Group II," respectively. Categorical and numerical data are expressed as ratio/proportions and mean (SD), respectively. Paired data from 43 participants (males 42 [97.7%]; age 32 [11] years) were analyzed. The pre-Tx and post-Tx LS of the entire cohort, measured at 307 (198) days of interval, were 8.5 (7.3) KPa and 6.7 (3.1) KPa, respectively. Before transplantation, 21 (49%) participants belonged to Group II and 22 (51%) to Group I. Among the Group II participants, 12 (57%) showed LS normalization after 312 (182) days of transplantation. Of the 22 participants in Group I, three (13.6%) showed LS elevation to >7.0 KPa after 303 (217) days of transplantation. The mean LS changes among the overall cohort, Group II, and Group I were -1.8 KPa, -4.1 KPa, and +0.2 KPa, respectively. LS in people on MHD may be falsely elevated, which is likely to normalize after successful renal transplantation.


Biomimetic synthesis of hybrid hydroxyapatite nanoparticles using nanogel template for controlled release of bovine serum albumin.
A biomimetic method was used to prepare hybrid hydroxyapatite (HAP) nanoparticles with chitosan/polyacrylic acid (CS-PAA) nanogel. The morphology, structure, crystallinity, thermal properties and biocompatibility of the obtained hybrid nanogel-HAP nanoparticles have been characterized. In addition, bovine serum albumin (BSA) was used as a model protein to study the loading and release behaviors of the hybrid nanogel-HAP nanoparticles. The results indicated that the obtained HAP nanoparticles were agglomerated and the nanogel could regulate the formation of HAP. When the nanogel concentration decreased, different HAP crystal shapes and agglomerate structures were obtained. The loading amount of BSA reached 67.6 mg/g for the hybrid nanoparticles when the mineral content was 90.4%, which decreased when the nanogel concentration increased. The release profile of BSA was sustained in neutral buffer. Meanwhile, an initial burst release was found at pH 4.5 due to the desorption of BSA from the surface, followed by a slow release. The hemolysis percentage of the hybrid nanoparticles was close to the negative control, and these particles were non-toxic to bone marrow stromal stem cells. The results suggest that these hybrid nanogel-HAP nanoparticles are promising candidate materials for biocompatible drug delivery systems.


Reversal of nitroglycerin tolerance in vitro by the cGMP-phosphodiesterase inhibitor zaprinast.
Following in vitro exposure of rat aortic rings to 550 microM nitroglycerin for 1 h, tolerance was demonstrated by a significant increase in EC50 values for nitroglycerin-induced relaxation. However, cross-tolerance to sodium nitroprusside was not observed. Co-incubation of aortic rings with the cGMP-phosphodiesterase (cGMP-PDE) inhibitor zaprinast (10 microM), during incubation with 550 microM nitroglycerin, did not prevent the development of tolerance. However, the addition of 0.30 or 10 microM zaprinast to tolerant aortic rings did restore responsiveness to nitroglycerin. The increase in cGMP in tolerant aortic rings in response to 300 nM nitroglycerin (2-4 fmol/micrograms) was significantly less than that observed for non-tolerant rings (6.6-12 fmol/micrograms), but cGMP levels were restored in tolerant rings by zaprinast (7-12 fmol/micrograms). These data suggest that inhibition of vascular cGMP-PDE activity does not prevent the development of tolerance in vitro, but does reverse the loss of vasorelaxant potency to nitroglycerin via restoration of intracellular cGMP levels.


Effect of human chorionic gonadotrophin on the dog seminiferous tubule, with and without experimental unilateral cryptorchism.
The effect on human chorionic gonadotrophin (HCG) on the testes of pubertal and postpubertal Beagle dogs was studied, in the one instance in bilaterally normotopic testes and in the other on the still scrotally located gonad of dogs which had been subjected to unilateral experimental cryptorchism. The area of the cross-sectioned seminiferous tubules served as a parameter for evaluating the effect of HCG. Administration of therapeutic doses of HCG produced, in animals with bilaterally normotopic testes, a marked diminution of the area of the seminiferous canals. This means that HCG application at normal dosage impairs the seminiferous tubules in the dog. In animals with unilateral cryptorchism, HCG application produced no significant change in the tubule area of the scrotally located testis beyond that which is ascertainable anyway on the orthotopic testis following translocation of the contralateral gonad to within the abdominal cavity. Hence, HCG does not influence the degenerative change in the orthotopic testis in experimental unilateral cryptorchism. Rather, an adverse effect of HCG on the seminiferous tubule is evident, independently of the hitherto published reports of successfully attained descent.


An update on the clinical pathology of oral precancer and cancer.
The identification of oral precancerous and cancerous lesions at an early stage allows for early intervention and minimizes mortality and morbidity. A combination of risk reduction and early detection should further reduce the incidence and improve outcomes. A clear understanding of the aetiology and clinical presentation of these lesions is key to effective management of these patients in primary dental care. We present a timely update on these issues, with an emphasis on the importance of early detection. The identification of lesions at precancerous stages or, at worst, early malignancy, is the key to better outcomes for our oral cancer patients.


Ontogenic isoform switching of UDP-glucuronosyltransferase family 1 in rat liver.
The liver undergoes dramatic changes in function during development. The development of UDP-glucuronosyltransferase family 1 (UGT1) isoforms was studied in livers from rats at 16-20days of gestation, at days 1, 2, 3, 4, and 7 of infancy, at days 14 and 28 of childhood, and at day 56 of young adulthood. We found developmental stage-specific switching of regulation of the rat UGT1 gene complex. UGT1A6 was expressed as a predominant component of UGT1 in fetus liver, while other UGT1 isoforms were repressed. In contrast, expression of UGT1A1 surged immediately after birth. Expression of UGT1A5 was transiently elevated in childhood. We also found age-dependent alternative usage of dual UGT1A6 promoters in rat liver. Since UGT1A1 is the only bilirubin-glucuronidating isoform, the ontogeny of UGT1A1 in liver microsomes demonstrates that inadequate UGT1A1 proteins in the early neonatal period are linked to the common etiology of idiopathic hyperbilirubinemia in the newborn infant.


Traumatic brain injury in a rural and an urban Tanzanian hospital--a comparative, retrospective analysis based on computed tomography.
In a resource-poor environment such as rural East Africa, expensive medical devices such as computed tomographic (CT) scanners are rare. The CT scanner at the rural Haydom Lutheran Hospital (HLH) in Tanzania therefore offers a unique chance to observe possible differences with urban medical centers in the disease pattern of trauma-related cranial pathologies. The purpose of this study was to compare traumatic brain injuries (TBIs) between a rural and an urban area of Tanzania. HLH has 350 beds and one CT scanner. The urban Aga Khan Hospital is a private hospital with 80 beds and one CT scanner. This was a retrospective study. Data of 248 patients at HLH and of 432 patients at Aga Khan Hospital with TBI could be collected. The prevalence of TBI was significantly higher in the rural area compared to the urban area (34.2% vs. 21.9%, P < 0.0001). TBI due to violence was noted to occur more frequently at HLH, whereas road traffic accidents were more frequent at the Aga Khan Hospital. The number of patients showing a normal CT result was significantly higher in the urban area (53.0% vs. 35.9%, P < 0.0001). Bone fractures (35.9% vs. 15.7%, P < 0.0001) and pneumocephalus (6.9% vs. 0.9%, P < 0.0001) were diagnosed significantly more frequently in the rural survey. Soft tissue swelling (11.6% vs. 1.2%, P < 0.0001) and frontal sinus injuries (7.4% vs. 0.4%, P < 0.0001) were observed significantly more often in the urban setting. This study documents the burden of TBI and the differences in TBI-related CT diagnoses and their incidence between urban and rural areas in Eastern Africa. These results are important as they demonstrate that patients with severe TBI are not a primarily urban concern. Management of TBI should be included in the training curricula for health personnel alike irrespective of whether their workplace is primarily urban or rural.


A small bowel volvulus caused by a mesenteric lipoma: report of a case.
A 31-year-old man underwent a laparotomy for acute intestinal obstruction symptoms, which he had intermittently experienced for 14 years. The cause of the obstruction was due to a volvulus of the small bowel caused by a mesenteric lipoma. This is a rare finding, which is ideally diagnosed by computed tomography, with surgery the best and most highly recommended treatment. This particular presentation, to the best of our knowledge, has not yet been previously reported in the English language.


Role of chicken fat waste and hydrogen energy ratio as the potential alternate fuel with nano-additives: Insights into resources and atmospheric remediation process.
The main focus of the study was to witness the effects of chicken waste-based biodiesel blends along with constant hydrogen injection in a modified diesel engine. Furthermore, the nanoparticle multiwall carbon nanotubes (MWCNT) effects on the engine efficiency were also examined. A series of tests was conducted in the single cylinder, water cooled engine fuelled with diesel, CB100N, CB10N, CB30N, and CB50N. Throughout the entire run, constant hydrogen injection of 5 LPM has been maintained. The parameters such as brake thermal efficiency, brake specific fuel consumption, heat release rate and the emissions of different pollutants were determined for a variety of engine speeds. ASTM standards were applied to measure the viscosity, density and calorific value. From the reported findings, it was clear that the addition of the chicken waste biodiesel could be a sustainable substitute for the existing fossil fuels. Although the emission of the pollutants was dropped significantly, there was a massive drop in the BTE values. To compensate such shortage of power, the biodiesel was dispersed with MWCNT at the concentration of 80 ppm. Compared to the regular biodiesel, MWCNT inclusion increased the BTE by 14%. Further, the consumption of the fuel was also reduced marginally. Considering the pollutants, the catalytic activity of the MWCNT reduced the emissions of CO, NOx, and HC at various engine speeds. Besides, 10% reduction in NOx had been reported at lower engine speeds and was reduced to 8% at higher speed regimes. Compiling all together, increasing the concentration of the biodiesel blends obviously reduced the performance values and however, there was a great advantage in terms of the emission magnitudes irrespective of the engine operating conditions.


The evolution and involution of Peyer's patches in fetal and postnatal sheep.
The Peyer's patches (PP) of sheep have a number of important anatomical features and functional characteristics which are similar to tissues that have been classified as primary lymphoid organs. The prenatal maturation of PP occurs in the absence of any antigenic stimulus as immunogenic molecules are not normally encountered by the sheep fetus. Primordial PP were first detected in the small intestine of fetal sheep at about 60-days gestation; lymphoid follicles were present by 75-days gestation and vigorous lymphopoiesis was occurring in these follicles by 100 days. From 120-days gestation until birth, at about 150 days, the PP follicles were histologically mature and they had the greatest density of proliferating lymphoid cells found anywhere in the body. The total number of PP and their constituent follicles had developed before birth when there were 25-40 discrete PP in the jejunum and proximal ileum and one single continuous PP in the terminal ileum. There was no evidence of any change in the rate of growth of the PP follicles at birth which could be related to the advent of the first antigens in the gut. The total weight of PP tissue was greater than any other single lymphoid tissue by about 6 weeks after birth weighing around 120 g or about 1.2% of the body weight; about 50-60 g of the PP tissue was calculated to be lymphoid tissue. At this time the ileocecal PP (IPP) extended 2.5 m along the terminal ileum and accounted for about 90% of the total mass of PP. From about 12 weeks after birth the IPP began to involute and only a few PP follicles remained in this region of the intestine by 18 months of age. Follicles in PP in other parts of the small intestine remained and continued to produce lymphocytes throughout the life of the animal. PP contain a number of anatomically and functionally distinct lymphoid compartments that could play different roles in the body's immune defense. Explicit in most theories on the function of PP is the notion that antigenic stimulation is the cause of the lymphopoiesis in the follicles; our results do not support this view. Instead they suggest that the follicles in the PP of sheep may play a role similar to that played by the bursa of Fabricius in birds.


Quantitative CT of Normal Lung Parenchyma and Small Airways Disease Topologies are Associated With COPD Severity and Progression.
Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients, and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline. PRM metrics of normal lung (PRMNorm) and functional SAD (PRMfSAD) were generated from CT scans collected as part of the COPDGene study (n=8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRMNorm and PRMfSAD. Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV1 decline using a machine learning model. Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRMfSAD and PRMNorm were independently associated with the amount of emphysema. Readouts χfSAD (β of 0.106, p<0.001) and VfSAD (β of 0.065, p=0.004) were also independently associated with FEV1% predicted. The machine learning model using PRM topologies as inputs predicted FEV1 decline over five years with an AUC of 0.69. We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRMfSAD and PRMNorm may show promise as an early indicator of emphysema onset and COPD progression.


Clinical Risk Management in radiology. Part I: general background and types of error and their prevention.
The present contribution, presented as an Editorial, addresses the issue of patient safety in Radiology: this topic, of great current National and Regional interest, has stimulated a strong focus on accidents and mistakes in medicine, together with the diffusion of procedures for Risk Management in all health facilities. The possible sources of incidents in the radiological process are exposed, due to human errors and to system errors connected both to the organization and to the dissemination of Information Technology in the Radiological world. It also describes the most common methods and tools for risk analysis in health systems, together with some application examples presented in Part II.


Properties of cutaneous acetyltransferase catalyzing N- and O-acetylation of carcinogenic arylamines and N-hydroxyarylamine.
The role of skin for N- and O-acetylations of carcinogenic arylamine and N-hydroxyarylamine was studied in vitro. Unexpectedly high activities were observed in acetyl CoA-dependent N-acetylations of 2-aminofluorene (2-AF) and p-aminobenzoic acid (PABA) in skin cytosols of hamsters. The specific activity for 2-AF (4.52 nmoles/mg protein per min) was largely the same as that of rat liver cytosols. The cutaneous cytosols also catalyzed N,N-acetyltransfer reaction from N-hydroxy-4-acetylamino-biphenyl (N-OH-AABP) to 2-AF and acetyl CoA-dependent O-acetylation of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1), suggesting that hamster skin cytosol has enzymes similar to hepatic acetyltransferases. In addition, remarkably high correlations were observed between the skin and liver in the activities for N-acetylations of PABA and 2-AF. In a colony of Syrian golden hamsters a clear polymorphism was detected in the cutaneous N-acetylations of PABA and 2-AF. These animals were divided into three groups according to their activities: rapid, intermediate and slow acetylators. On the other hand, the acetylating activities in the skin and liver of these three groups showed monomorphic distribution with N-OH-AABP-dependent N,N-acetyltransfer of 2-AF and acetyl CoA-dependent O-acetylation of N-OH-Glu-P-1. These results, together with the detection of N-acetylating activity in the skin of other experimental animals and humans, suggest that skin may play an important role in the metabolism of aromatic amines and that the cutaneous acetylation in hamsters may be under the common genetic control which regulates the individual difference in the hepatic activities.


Congenital synmastia with concurrent fibroadenomas in a pediatric patient.
Congenital synmastia, or absence of the intermammary sulcus, is a rare breast anomaly in the pediatric population. While acquired synmastia after breast augmentation is a well-documented entity, congenital synmastia is a rare condition with only four previous cases reported in the surgical literature. We describe the first patient with concurrent presentation of congenital synmastia and multiple fibroadenomas. A combined technique was used to both address the patient's breast lesions and correct the defect.


A 1H-NMR study of bilirubin IX alpha solubilization by cholate micelles: application of nuclear Overhauser effects.
The solubilization of bilirubin IX alpha in aqueous solution by sodium cholate micelles has been examined by 270 MHz 1H-NMR spectroscopy. Incorporation of bilirubin into the micelles is accompanied by specific shifts of bilirubin vinyl and bridgehead protons and the C18 and C19 methyl groups of the steroid. The observed chemical shifts show a monotonic concentration dependence suggesting that changes in aggregation size are continuous. Nuclear Overhauser effects (NOE) have been shown to be a useful probe or micellization. A 4:1 cholate/bilirubin mixture has been investigated by difference NOE spectroscopy. The observation of intermolecular nuclear Overhauser effects between peripheral protons of bilirubin and cholate are diagnostic of spatially proximate groups. Inter-cholate nuclear Overhauser effects increase in magnitude upon bilirubin incorporation suggesting closer packing of steroid molecules on solubilization of the pigment. Intramolecular nuclear Overhauser effects observed for solubilized bilirubin are consistent with a compact intramolecularly hydrogen-bonded conformation resembling that determined for bilirubin in the solid state.


Coronary provocative tests in the catheterization laboratory: Pathophysiological bases, methodological considerations and clinical implications.
The paradigm for the management of patients presenting with angina and/or myocardial ischemia has been historically centered on the detection and treatment of obstructive coronary artery disease (CAD). However, in a considerable proportion (30-50%) of patients undergoing coronary angiography, obstructive CAD is excluded. Thus, functional mechanisms may be involved in determining myocardial ischemia and should be investigated. In particular, coronary vasomotor disorders both at epicardial and at microvascular level may play a crucial role, but a definitive diagnosis of these disorders can at times be difficult, given the transience of symptoms, and often requires the use of coronary provocative tests. Of importance, these tests may provide relevant information on the pathogenic mechanism of myocardial ischemia, allowing physicians to tailor the therapies of their patients. Furthermore, several studies underscored the important prognostic information deriving from the use of coronary provocative tests. Nevertheless, their use in clinical practice is currently limited and mainly restricted to specialized centers, with only a minority of patients receiving a benefit from this diagnostic approach. In this review, we explain the pathophysiological bases for the use of provocative tests, along with their clinical, prognostic and therapeutic implications.


Do socioeconomic gradients in women's health widen over time and with age?
A population-based study was conducted to investigate changes over time in women's well-being and health service use by socio-economic status and whether these varied by age. Data from 12,328 mid-age women (aged 45-50 years in 1996) and 10,430 older women (aged 70-75 years) from the Australian Longitudinal Study on Women's Health were analysed. The main outcome measures were changes in the eight dimensions of the Short Form General Health Survey (SF-36) adjusted for baseline scores, lifestyle and behavioural factors; health care utilisation at Survey 2; and rate of deaths (older cohort only). Cross-sectional analyses showed clear socioeconomic differentials in well-being for both cohorts. Differential changes in health across tertiles of socioeconomic status (SES) were more evident in the mid-age cohort than in the older cohort. For the mid-aged women in the low SES tertile, declines in physical functioning (adjusted mean change of -2.4, standard error (SE) 1.1) and general health perceptions (-1.5, SE 1.1) were larger than the high SES group (physical functioning -0.8 SE 1.1, general health perceptions -0.8 SE 1.2). In the older cohort, changes in SF-36 scores over time were similar for all SES groups but women in the high SES group had lower death rates than women in the low SES group (relative risk: 0.79, 95% confidence interval 0.64-0.98). Findings suggest that SES differentials in physical health seem to widen during women's mid-adult years but narrow in older age. Nevertheless, SES remains an important predictor of health, health service use and mortality in older Australian women.


Luminescent and magnetic Fe3O4/Py/PAM nanocomposites for the chromium(VI) determination.
A novel luminescent and magnetic Fe(3)O(4)/pyrene/polyacrylamide (Fe(3)O(4)/Py/PAM) nanocomposite has been prepared under ultrasonic radiation. This magnetic nanocomposite combined with pyrene would lead to a special functional magnetic luminescent composite that enjoys both the advantages of magnetic nanoparticles of Fe(3)O(4) and fluorescence nanoparticles of pyrene. Taking advantage of the magnetic property of Fe(3)O(4) nanocomposites, we can separate Fe(3)O(4)/Py/PAM nanocomposites from solution easily just by using a permanent magnet. Based on the fluorescence quenching of Fe(3)O(4)/Py/PAM nanocomposites by Cr(VI), a method for the selective determination of Cr(VI), without separation of Cr(III) in water, was developed. Under optimal experimental conditions, a limit of detection of 0.01 microg mL(-1) was achieved. The calibration curve was linear over the concentration range of 0.1-14.0 microg mL(-1) with a correlation coefficient of 0.9975. The proposed method has been applied to the selective quantification of Cr(VI) in synthetic samples and wastewater samples with the satisfactory results.


Hepatic angiosarcoma associated with short-term arsenic ingestion.
In a 45 year old man, hepatic angiosarcoma developed 33 years after medicinal arsenic ingestion of only six months' duration. In addition, the patient had a history of basal cell carcinomas without having had excessive sunlight exposure. Factor VIII staining of the tumor supports an endothelial cell origin of the tumor. The development of skin cancers and hepatic angiosarcoma in this patient suggests that there may be no safe threshold of arsenic exposure. A careful history concerning even short-term arsenic exposure in all patients with hepatic angiosarcoma may uncover more examples of this association.


Myelination of regenerating optic nerve axons occurs in conjunction with an increase of the oligodendrocyte precursor cell population in the adult mice.
Recently, regeneration of CNS tracts has been partially accomplished by strategies of intrinsic neuronal growth stimulation. However, restoration of function is dependent on proper myelination of regenerating axons. Previous work from our group (Goulart et al., 2018) has shown an increase in oligodendrocyte staining in the regenerating optic nerve, 2 weeks after crush, in animals that were submitted to conditional deletion of pten gene in retinal ganglion cells and intravitreal injection of zymosan + cAMP. Thus, in the present study we aimed to investigate the maturation of the oligodendroglial lineage and myelination during the regeneration of the optic nerve under the same conditions of our previous work. We showed that the combined treatment promoted an increase of myelinated fibers within the optic nerve, 12 weeks after lesion, as well as an increase in Sox10 positive cells. Early-OPCs, positive to A2B5, were also increased at 12 weeks, whereas O4 positive, late-OPCs, were increased from 2 until 12 weeks after crush. At 12 weeks after crush, the optic nerve of Regenerating group presented more CC1 positive oligodendrocytes and increased MRF positive myelinating oligodendrocytes, culminating in CTB traced regenerating axons superimposed to MBP staining, suggestive of myelination. Thus, our work showed that conditional deletion of pten gene in retinal ganglion cells and intravitreal inflammatory stimuli + cAMP stimulate full maturation of the olidodendroglial lineage, from OPC proliferation and differentiation to myelination of regenerating CNS axons.