Vasoactive properties of antidepressant N-alkyl derivatives.
Hypotension is a principal side effect of antidepressant therapy. In addition to serotonin and noradrenalin reuptake inhibition, some antidepressants have shown ion channel interactions which are thought to be related to the vascular effects of these agents. Methylation of the pharmacophore has shown to change the pharmacological properties of a variety of compounds. The purpose of this work was to evaluate whether methylation of the amino group of imipramine (TCA's) and fluoxetine (SSRI) could change their vasodilator properties. N-methyl imipramine (NMI), N-methyl fluoxetine and (NMF) N-N dimethyl fluoxetine (NNDF) were synthesized and compared with desipramine (DES), imipramine (IMI) and fluoxetine (F) in their ability to relax rat aortic rings pre-contracted with 80mM KCl using an isolated bath preparation. Drugs were evaluated in thoracic aorta rings with and without endothelium. All compounds displayed a vasorelaxant effect. Endothelium-denuded aortic rings showed an increased relaxant response for IMI and derivatives compared with endothelium-intact vessels, while no endothelium-dependent effect was observed with F and its methyl derivatives. Maximal relaxant potency was displayed by dimethylated derivatives (IMI and NMF), while NMI in the TCA series and NNDF in the SSRI series (both with 3 methyl groups), had the least potency to relax either preparation. Endothelium plays an important role inhibiting the vasodilatation induced by IMI and its derivatives. Vascular relaxation is increased in the compounds tested with 2 methyl groups in their structure, while the presence of 3 methyl groups (positive charge) importantly reduced the relaxant potency.


Advances in traction methods for endoscopic submucosal dissection: What is the best traction method and traction direction?
Endoscopic submucosal dissection (ESD) has been developed as a treatment for superficial gastrointestinal neoplasms, which can achieve en bloc resection regardless of the lesion size. However, ESD is technically difficult because endoscopists cannot bring their hand into the gastrointestinal tract, unlike surgeons in regular surgery. It is difficult to obtain sufficient tension in the dissection plane and a good field of vision. Therefore, ESD is associated with a long procedure time and a high risk of adverse events in comparison with endoscopic mucosal resection. Traction methods have been developed to provide sufficient tension for the dissection plane and a good field of vision during the ESD procedure. However, traction direction is limited in most traction methods, resulting in insufficient effect in some cases. Although traction direction is considered important, there have been few investigations of its effect. In the first half of this review, important traction methods are discussed, including traction direction. In second half, appropriate traction methods for each organ are considered. Other important considerations for traction method, such as ability to adjust traction strength, interference between traction device and endoscope, and the need for specialized devices are also discussed.


What do hormones have to do with aging? What does aging have to do with hormones?
It is clear that aging results in alterations of endocrine physiology, which in turn appear to contribute to development of the senescent phenotype. How the underlying basic aging process or processes cause the endocrine cell dysfunctions leading to hormone imbalance is far from clear, but oxidative alteration of cell membranes is an attractive candidate mechanism that might be susceptible to some degree of global remediation.


Vitamin A-induced synthesis of alkaline phosphatase.
Incorporation of radioactive leucine into electrophoretically separated proteins from mouse tail epidermis indicates that synthesis of alkaline phosphatase is stimulated by vitamin A. It is suggested that some of the diverse effects of vitamin A may be the result of alkaline phosphatase induction.


Deuteration-induced scission of C58 oligomers.
The reaction of solid C(58) films with atomic deuterium to yield deuterofullerenes, C(58)D(x), has been investigated by thermal desorption spectroscopy coupled with mass spectrometric detection, ultraviolet photoionization spectroscopy (21.2 eV), and atomic force microscopy (AFM). The average composition of the deuterofullerenes created depends on deuterium dose, beam flux, and surface temperature. Low deuterium exposures at room temperature yield predominantly C(58)D(6-8) cages. Saturation exposures at room temperature yield mass spectra peaked at C(58)D(26). After saturation exposures at elevated surface temperatures (approximately 500 K), the (subsequently) desorbed material reveals a comparatively narrow mass spectral distribution centered at C(58)D(30). Deuteration is associated with cleavage of covalent cage-cage bonds in the starting C(58) oligomer material, as evidenced by a considerable lowering of the sublimation energies of C(58)D(x) compared to desorption of C(58) desorbed from pure oligomer films. Correspondingly, AFM images reveal a D-induced, thermally activated transition from dendritic C(58) oligomer islands into smooth-rimmed islands composed of deuterated cages. Deuterated films exhibit a significantly lower work function than bare C(58) films. Progressing deuteration also gradually raises the surface ionization potential.


Methods for analyzing and quantifying protein-protein interaction.
Genome sequencing has led to the identification of many proteins, which had not been recognized before. In consequence, the basic set of human proteins is generally known. Far less information, however, exists about protein-protein interactions, which are required and responsible for cellular activities and their control. Many protein isoforms that result from mutations, splice-variations and post-translational modifications also come into play. Until recently, interactions of only few protein partners could be analyzed in a single experiment. However, this does not meet the challenge of investigating the highly complex interaction patterns in cellular systems. It is made even more demanding by the need to determine the intensity of interactions quantitatively in order to properly understand protein interplay. Currently available techniques vary with respect to accuracy, reliability, reproducibility and throughput and their performances range from a mere qualitative demonstration of binding to a quantitative characterization of affinities. In this article, an overview is given of the methodologies available for analysis of protein-protein interactions.


Parents' reports of the body shape and feeding habits of 36-month-old children: an investigation of gender differences.
The current study examined parental perception of offspring body shape, differential reporting of offspring eating behaviors by mothers and fathers, and gender-specific patterns of offspring feeding habits. Parents of a community sample of 36-month-old children (N = 93) completed measures regarding their offspring's feeding patterns and body shape. Results revealed noteworthy correlates (e.g., concerns about their child's appetite) of parental perception of offspring weight status. They further suggested that mothers and fathers often differed in their accounts of their child's eating habits, and that parents report certain eating behaviors differently depending on the gender of their child. Clinical and theoretical implications are discussed.


Pd@Ag Nanosheets in Combination with Amphotericin B Exert a Potent Anti-Cryptococcal Fungicidal Effect.
Silver nanoparticles have received considerable interest as new "nanoantibiotics" with the potential to kill drug-resistant microorganisms. Recently, a class of new core-shell nanostructures, Pd@Ag nanosheets (Pd@Ag NSs), were created using deposition techniques and demonstrated excellent inhibitory effects on various bacteria in vitro. In this study, we evaluated the antifungal activity of Pd@Ag NSs against common invasive fungal pathogens. Among these organisms, Cryptococcus neoformans complex species was most susceptible to Pd@Ag NSs, which exhibited potent antifungal activity against various molecular types or sources of cryptococcal strains including fluconazole-resistant isolates. The anticryptococcal activity of Pd@Ag NSs was significantly greater than fluconazole and similar to that of amphotericin B (AmB). At relatively high concentrations, Pd@Ag NSs exhibited fungicidal activity against Cryptococcus spp., which can likely be attributed to the disruption of cell integrity, intracellular protein synthesis, and energy metabolism. Intriguingly, Pd@Ag NSs also exhibited strong synergistic anti-cryptococcal fungicidal effects at low concentrations in combination with AmB but exhibited much better safety in erythrocytes than AmB, even at the minimal fungicidal concentration. Therefore, Pd@Ag NSs may be a promising adjunctive agent for treating cryptococcosis, and further investigation for clinical applications is required.


Isolation and characterization of a variant myoblast cell line that is temperature sensitive for differentiation.
A new variant rat myogenic cell line, ts485, was isolated by subcloning the cell line ts3b2 (H. T. Nguyen, R. M. Medford, and B. Nadal-Ginard, Cell 34:281-293, 1983). Unlike the progenitor cell line, ts485 was thermosensitive for differentiation. Experiments with conditioned medium suggested that diffusible extracellular factors were not involved in dictating the differential phenotypes of ts485 cells cultured at the permissive and nonpermissive temperatures. Temperature shift experiments performed on cultures of ts485 cells indicated that the temperature-sensitive lesion was in a factor active during the growth phase and required to trigger a cascade of events leading to terminal differentiation.


A Bi-LSTM and multihead attention-based model incorporating radiomics signatures and radiological features for differentiating the main subtypes of lung adenocarcinoma.
The radiological features of computed tomography (CT) images and the sequence of radiomics signatures in continuous slices of lung CT lesions are helpful in identifying subtypes of lung adenocarcinoma. A model based on bidirectional long short-term memory (Bi-LSTM) and multihead attention can learn the rules of this sequence well. In this study, 421 patients with 427 lesions confirmed as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) or invasive adenocarcinoma (IAC) were recruited from three hospitals. The radiomics signatures of the identified lesion regions in each CT image were extracted using 'PyRadiomics' software, and the corresponding radiological features were subsequently documented and collected. Then, the top 100 features were extracted by the minimum redundancy maximum relevance (mRMR) feature ranking method. A model based on the radiological and imaging features was established to classify the lesions using Bi-LSTM and multihead attention. The diagnostic performance of the model was measured by the area under the curve (AUC) of the receiver operating characteristic (ROC). The model combined radiological features and radiomics signatures. The AUCs of the model in the training, testing, and validation groups were 0.985, 0.94 and 0.981, respectively, and the accuracy was 0.92, 0.976 and 0.91, respectively. In addition, we trained two other models [convolutional neural network (CNN) + multihead attention, long short-term memory (LSTM) + multihead attention] and compared them using the testing dataset. The precision of the two models was 0.89 and 0.88, respectively, and the accuracy was 0.88 and 0.87, respectively. Bi-LSTM and multihead attention based on radiomics signatures and radiological features provide a way to distinguish AIS, MIA, and IAC.


Hyperoxia may reduce energetic efficiency in the trained rat.
Several studies have been conducted in recent years in the attempt to improve running performance by the use of hyperbaric oxygen, but there is disagreement as to whether this has any beneficial effect. The purpose of this study was to measure the effect of 24 h breathing 100% O2 in normobaric conditions on energetic efficiency in the trained rat. Experiments were carried out on trained rats whose oxygen consumption was evaluated during the training period and on its completion. At the end of the training period, the rats were divided into two groups: 1) rats exposed to air (21% O2) in normobaric conditions; and 2) rats exposed to 100% O2 in normobaric conditions. In addition, two groups of sedentary rats were used: 3) sedentary rats exposed to air (21% O2) in normobaric conditions; and 4) sedentary rats exposed to 100% O2 in normobaric conditions. Energetic efficiency was estimated by measuring O2 consumption at submaximal exercise (45 m.min-1, 10 degrees incline). Training alone reduced O2 consumption by 18% during submaximal exercise. Exposure to 100% oxygen for 24 h in normobaric conditions reversed the effect of complete training by elevating the O2 consumption by 17%, which was close to the oxygen consumption of the rats during the incomplete training period. Our results suggest that prolonged exposure to hyperoxia induces a reduction in the energetic efficiency of the trained rat. The relevance of these findings to sports and diving is discussed.


Photo-induced structural modification of silk gels containing azobenzene side groups.
Azobenzene modification of Bombyx mori silkworm silk creates a photo-responsive 'azosilk' biomaterial, allowing for 3D laser patterning. Written regions fluoresce, and become fluid-filled raised 'micro-blisters' with a 10-fold photo-softening effect of the modulus. Patterning is facile and versatile, with potential applications as soft tunable materials for dynamic cell guidance and microfluidics.


Genetic screening for MEN1 mutations in families presenting with familial primary hyperparathyroidism.
A large number of families with familial isolated hyperparathyroidism (FIHP) have been reported. We wanted to determine if some of these families represent early manifestations of full-blown syndromes such as multiple endocrine neoplasia type 1 (MEN-1), as early identification may alter surgical and medical management. Four small families with a family history of hyperparathyroidism without clear-cut MEN-1 features were screened for a MEN1 mutation. The 10 exons of the MEN1 gene were amplified and analyzed by single-strand conformation analysis (SSCA). Abnormal SSCA shifts were then sequenced using an automated sequencer. Two germline mutations were found: R527X and P277H. The former was detected in three members of a family consisting of two children and a mother. At the time of testing the youngest son was normocalcemic and clinically normal but subsequently developed hyperparathyroidism (HPT). Since the initial testing, the family has been confirmed to be a MEN-1 family as the mother has developed abdominal pain and an elevated serum pancreatic polypeptide and the younger brother an anterior pituitary tumor and recurrent HPT. The latter P277H mutation was identified in two of three members tested from another family. Manifestations of MEN-1 syndrome have also developed. The father now has developed diarrhea and elevated serum gastrin; and the daughter has developed recurrent HPT. Genetic screening of families who clinically have FIHP is important and may influence the type of medical and surgical treatment and follow-up, as some have MEN-1 syndrome. Long-term screening for MEN syndromes should be included in this set of patients. Positive screening may predict disease and allow early detection and appropriate treatment before initiation of symptoms.


Hyperintensity in the subarachnoid space on FLAIR MRI.
The purposes of this essay are to illustrate the causes of FLAIR hyperintensity in the subarachnoid space and to outline the mechanisms of the findings. FLAIR subarachnoid space hyperintensity may be encountered with both pathological conditions and artifacts. Knowledge of these conditions and appearances coupled with any associated findings may suggest the cause of the FLAIR subarachnoid space hyperintensity. A diffuse distribution and a lack of ancillary findings often remain nonspecific and may require clinical correlation and CSF analysis.


Impact of National Clinical Guideline recommendations for revascularization of persistently occluded infarct-related arteries on clinical practice in the United States.
The Occluded Artery Trial (OAT) was a large, randomized controlled trial published in 2006 that demonstrated no benefit to routine percutaneous coronary intervention (PCI) of persistently totally occluded infarct-related arteries (IRA) identified a minimum of 24 hours (on calendar days 3-28) after myocardial infarction (MI). The purpose of this study was to determine the impact of OAT results and consequent change in guideline recommendations for PCI for treatment of persistently occluded IRAs. We identified all patients enrolled in the CathPCI Registry, from 2005 to 2008, undergoing catheterization more than 24 hours after MI with a totally occluded native coronary artery and no major OAT exclusion criteria. We examined trends in monthly rates of PCI for occlusions after OAT publication and after guideline revisions. Because reporting of diagnostic catheterizations was not mandatory, we examined trends among hospitals in the highest quartile for reporting of diagnostic procedures. A total of 28,780 patient visits from 896 hospitals were included. Overall, we found no significant decline in the adjusted monthly rate of PCI of occlusions after publication of OAT (odds ratio [OR], 0.997; 95% confidence interval [CI], 0.989-1.006) or after guideline revisions (OR, 1.007; 95% CI, 0.992-1.022). Among hospitals consistently reporting diagnostic catheterizations, there was no significant decline after OAT publication (OR, 1.018; 95% CI, 0.995-1.042), and there was a trend toward decline after guideline revisions (OR, 0.963; 95% CI, 0.920-1.000). These findings suggest that the results of OAT and consequent guideline revisions have not, to date, been fully incorporated into clinical practice in a large cross-section of hospitals in the United States.


Design of broadband linear micromachined ultrasonic transducer arrays by means of boundary element method coupled with normal mode theory.
In view of the maturity of fabrication processes for capacitive micromachined ultrasonic transducers (cMUTs), engineers and researchers now need efficient and accurate modeling tools to design linear arrays according to a set of technological specifications, such as sensitivity, bandwidth, and directivity pattern. A simplified modeling tool was developed to meet this requirement. It consists of modeling one element as a set of cMUT columns, each being a 1-D periodic array of cMUTs. Model description and assessment of simulation results are given in the first part of the paper. The approach is based on the theory of linear systems so the output data are linked to input data through a large matrix, known as an admittance matrix. In the second part of the paper, we propose reorganization of matrix equations by applying the normal mode theory. From the modal decomposition, two categories of eigenmodes are highlighted, one for which all cMUTs vibrate in phase (the fundamental mode) and the others, which correspond to localized subwavelength resonances, known as baffle modes. The last part of the paper focuses mainly on the fundamental mode and gives several design strategies to optimize the frequency response of an element.


[Persistence of the treatment of overactive bladderin Czech Republic].
Overactive bladder is chronic disease with high prevalence rate (9-42%). This syndrome requires longterm therapy but the persistence of this treatment in comparison with other chronic diseases as diabetes, hypertension, osteoporosis etc. is low. Accorging many studies the persistence variability is high and could be influenced by regional circumstanses. We desided to analyze real situation in parasympatolytics persitance in two years period in Czech Republic based on registry of health insurance company. We analyzed data between 2009 and 2010 of all clients of health insurance company where they fullfil their prescribtion. We analyzed the persistence in one year period in different periods of the year and within one year. In comparison of the same period between those two year there was a trend of increase of prescription but it was not significant: 1306(SD 56.3) vs 1410 (SD 68.1) - p = 0.056. Prescription of the treatment after one year was only 18.5%(min. 16.8 - max. 20.4, SD 1.56). Major drop-out was in first 3-month period where renewed their prescription only 25.9% of the patients. This one of the first study analyzing the parasympatolytics prescription persistence based on registry of health insurence company. The persistence in Czech Republic was low but withing the range of international data. Those result should be used as a reference data for comparison of the effect of varius strategies influencing the overactive bladder treatment.


Difference in release kinetics of unwashed and washed platelet-released supernatants from bone substitute materials: the impact of platelet preparation modalities.
In regenerative dentistry, platelet preparations are applied to stimulate bone healing and periodontal regeneration. Here, we pursue a strategy where bone substitutes are used as carriers for platelet-released supernatants. The mitogenic capacity and release kinetics of loaded bone substitutes were assessed. Platelet-released supernatants of washed platelets (washed PRS) and platelet-released supernatants of unwashed platelets (unwashed PRS) were lyophilized onto the bone substitutes deproteinized bovine bone mineral, hydroxyapatite and β-tricalcium phosphate. Scanning electron microscopy images were taken. Supernatants of bone substitutes were collected at hours 1, 3, 6, 24, and 48 and medium was replaced. We evaluated the protein content with the bicinchoninic acid assay and the effect on proliferation using bioassays with human periodontal fibroblasts. Release of growth factors from the loaded bone substitutes was measured based on the platelet-derived growth factor isoform (PDGF-BB) and thrombin immunoassays. Furthermore, we assessed DNA and RNA content of washed PRS and unwashed PRS. Unwashed PRS showed higher total protein concentrations than washed PRS, while the concentration of PDGF-BB, thrombin, DNA, RNA and their mitogenic effect was not significantly different. The bone substitute materials adsorbed protein over time but no significant changes in overall appearance was found. Supernatants collected from unwashed PRS-loaded bone substitute after 1 h induced a potent mitogenic response in periodontal fibroblasts. This pro-mitogenic capacity of the supernatants decreased over the observation period. Supernatants of washed PRS-loaded bone substitutes did not induce a substantial mitogenic effect. Levels of PDGF-BB, thrombin and protein were higher in supernatants of unwashed PRS-loaded bone substitutes than of washed PRS-loaded bone substitutes. Bone substitutes loaded with unwashed PRS, but not bone substitutes loaded with washed PRS show continuously declining release kinetics. These data suggest that plasma components in platelet preparations can modify the release kinetics profile.


Synthesis and anti-inflammatory properties of 1,2-dialkoxy-4-(3-dimethylaminopropionyl)benzenes and their 5-halogeno derivatives.
A series of new 1,2-dialkoxy-4-(3-dimethylaminopropionyl)benzene hydrochlorides and their 5-halogeno derivatives were synthesized and studied for anti-inflammatory properties. The diethoxy and dipropoxy derivatives were more active than the dimethoxy derivative and previously reported heterocyclic analogues. The introduction of a halogeno substituent at the 5-position of the dimethoxy derivative aromatic ring potentiated the activity. The 5-bromo derivative was more active than 5-chloro and 5-fluoro derivatives. Anti-inflammatory and analgesic effects of the 5-bromo derivative were less pronounced than those of indomethacin but greater than those of lysine acetylsalicylate (LAS). The 5-bromo derivative was more toxic than LAS but possessed similar gastrotoxicity. This compound was significantly less toxic and significantly less gastrotoxic than indomethacin++. Therapeutic indices of the 5-bromo derivative were significantly greater than those of LAS and indomethacin.


Sex steroids and epidermal glands in two species of gekkonine lizards.
In vivo and in vitro experiments on the endocrine relationships of epidermal glands in the tokay Gekko gecko, and the common house gecko Hemidactylus bowringii are reported. The results show that certain aspects of beta-gland differentiation involve a synergistic action between androgens and those hormones responsible for controlling the normal shedding cycle, while other aspects are solely under androgenic control. Pre-anal organ activity appears to be solely under androgenic control.


Estimation of intracellular sugar phosphate concentrations in Saccharomyces cerevisiae using 31P nuclear magnetic resonance spectroscopy.
A systematic procedure has been formulated for estimating the relative intracellular concentrations of sugar phosphates in Saccharomyces cerevisiae based upon (31)P nuclear magnetic resonance (NMR) measurements. The sugar phosphate region of the (31)P NMR spectrum is first decomposed by computer analysis, and the decomposition consistency and identification of individual sugar phosphate resonances are established based on in vitro chemical shift calibrations determined in separate experiments. Numerous evaluations of intracellular S. cerevisiae compositions for different strains and different cell environments provide the basis for in vivocorrelations of inorganic phosphate chemical shift with the chemical shifts of 3-phosphoglycerate, beta;-fructose 1,6-diphosphate, fructose 6-phosphate, and glucose 6 phosphate. Relative intracellular sugar phosphate concentrations are obtained by correcting peak areas for partial saturation during transient in vivo experiments. In vivo concentrations estimated by this method agree well with estimates for similar systems based on other techniques. This approach does not require costly la belled compounds, and has the advantage that other important metabolic state variables such-as internal and external pH and intracellular levels of phosphate, ATP, ADP, NAD(H), and polyphosphate may be determined from the same (31)P spectrum. Extension of this strategy to other cellular systems should be straightforward.


Obliterative arteriosclerosis of extremities in patients with coronary heart disease.
In a group of 314 patients after past myocardial infarction or an episode of acute coronary insufficiency, angiological examination, repeated after a one-year interval, was performed. In the first examination, signs of obliterative arteriosclerosis in the lower extremities were found in 18.8% of the patients. It was noteworthy that 34% of patients with peripheral obliterative arteriosclerosis had no complaints connected with an impairment of circulation in the limbs. On the basis of the second examination, performed after a one-year interval, it was found that the annual incidence of obliterative arteriosclerosis in the lower extremities was 7.4%. In 66% of patients showing signs of obliterative arteriosclerosis at the first examination, objective impairment of peripheral circulation was observed after a one-year interval. In none of the patients did the investigators find signs of obliterative arteriosclerosis in the upper extremities.


Initial use of subcutaneous plasma-derived C1 inhibitor in prophylaxis of acute attacks of hereditary angioedema in pregnant patients in Slovakia.
Hereditary angioedema (HAE) is a rare, inborn disease manifested with recurrent attacks of angioedema. They can affect the skin and subcutaneous tissue, mucous membranes (gastrointestinal, respiratory, and uropoietic tracts), and submucous tissue. Women in reproductive age require specific management of the disease regarding both the course of the disease and treatment options. It is not only the treatment in female patients that is specific, but also the situations (pregnancy, breastfeeding). We present a case report of the initial use of a subcutaneous C1 inhibitor in the long-term prophylaxis of HAE attacks in two pregnant patients.


Urinary excretion of mefenamic acid and its metabolites including their esterglucuronides in preterm infants undergoing mefenamic acid therapy.
Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.


Safety of orbital atherectomy in patients with left ventricular systolic dysfunction.
We evaluated the angiographic and clinical outcomes in patients with severely calcified lesions and systolic dysfunction who underwent orbital atherectomy (OA). We hypothesized that OA would provide similar outcomes in patients with systolic dysfunction compared with patients with preserved systolic function. Systolic dysfunction is associated with an increased risk of adverse clinical events after percutaneous coronary intervention (PCI). The effects of OA in patients with systolic dysfunction are unknown. Our analysis retrospectively analyzed 438 patients (n = 69 with EF ≤ 40%) who underwent OA. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCE) at 30 days. There were no significant differences between patients with preserved versus reduced systolic function in terms of dissections (0.9% vs. 1.6%, P = 0.51), perforation (0.3% vs. 3.2%, P = 0.07), or no reflow (0.3% vs. 3.2%, P = 0.07). Patients with systolic dysfunction had higher rates of the composite of 30-day MACCE (1.1% vs. 8.7%, P = 0.002) and the individual end points of death (0.3% vs. 7.2%, P < 0.001), and myocardial infarction (0.5% vs. 4.3%, P = 0.03). The rates of target vessel revascularization (0% vs. 0%, P = 1), stroke (0.3% vs. 0%, P > 0.9), and stent thrombosis (0.8% vs. 1.4%, P = 0.5) were low in both groups and did not differ. Plaque modification with OA was safe and well tolerated in patients with systolic dysfunction. In this high-risk cohort, adverse clinical outcomes occurred more frequently than in a lower risk population.


A study of the main determinants of kidney allograft long-term survival in the era of new immunosuppressive drugs.
The outcome of long-term kidney allograft is extremely important. The present study aimed to discern the factors affecting long-term kidney allograft survival, including the type of donation and the use of extended criteria donors. Seven hundred and thirty-seven kidney transplant alone patients entered this retrospective cross-sectional study. The impact of different factors on death-censored long-term kidney allograft survival was evaluated. The Cox proportional survival model was employed to identify these factors. A value of P < 0.05 was considered statistically significant. The data were analyzed using IBM Statistical Package for the Social Sciences version 19.0. The study was conducted at the Mashhad University of Medical Sciences, Mashhad, Iran. In comparison with living kidney donations, both nontraumatic and traumatic brain death cadaveric kidney donations showed statistically significant inferior graft survival. Furthermore, the Kaplan-Meier survival analysis showed better durability of living kidney donations in comparison with traumatic and nontraumatic deceased donors (Log-rank test value = 0.001). Patients with delayed graft function (DGF) had a significantly shorter long-term death censured long-term graft survival in comparison with those without this complication. The Cox proportional models showed that DGF occurrence and the type of donation play a statistically significant role in long-term kidney graft survival. In addition, regarding graft survival, there was no difference between standard criteria and extended criteria donors. The occurrence of DGF and living or deceased types of donations have a significant effect on long-term kidney allograft survival.


Triggering learning in midwifery.
The delivery of the head with or without forceps may have been quite easy, but more commonly there has been a little difficulty in completing the extension of the head. The hairy scalp slides with reluctance. When the forehead has appeared it is necessary to press back the perineum to deliver the face. Fat cheeks eventually emerge. A double chin has hooked over the posterior commissure, to which it remains tightly opposed. Restitution seldom occurs spontaneously for the head seems incapable of movement as a result of friction with the girdle of contact at the vulva... time passes. The child's face becomes suffused. It endeavours unsuccessfully to breathe. Abdominal efforts by the mother or by her attendants produce no advance, gentle traction is equally unavailing... Usually equanimity forsakes the attendants. They push, they pull. Alarm increases. Eventually, by greater strength of muscle or some infernal struggle, the difficulty seems to be overcome... It dawns upon the attendants that their anxiety was not ill founded.


[Screening and confirmation of anti-HCV antibodies in Tunisian blood donors].
Antibodies to Hepatitis C virus (HCV) were tested in 43000 Tunisian blood donors by using enzyme immuno-assay. Our results show that 0.7% (304/43000) were anti-HVC positive. Of these 304.78 were confirmed anti-HCV positive (0.18%) by immuno-blot, and 99 displayed an indeterminate profile. Different immune responses were observed: In donors with positive serologic pattern (78/304), 25.6% response towards whole antigens (C + NS3 + NS4 + NS5) was frequently observed (44/78) 56.4%. Reactivity to 2 antigens was observed in 28.2% (22/78) and with 3 antigens in only 15.4% (12/78), with systematic reactivity to core. In donors with indeterminate serologic pattern (99/304) 32.5%, reactivity to non-structural antigen NS5 was the most frequently observed (54/99) 54.5%, reactivity to non-structural NS3 antigen was noted in 27.3% (27/99) and to core antigen in 18.2% (18/99). No donors with isolated reactivity to NS4 were observed in our series.


BUTTERFLY WING MARKINGS ARE MORE ADVANTAGEOUS DURING HANDLING THAN DURING THE INITIAL STRIKE OF AN AVIAN PREDATOR.
The "false head" hypothesis states that due to the posterior ventral wing markings of certain butterflies which resemble a "false head," visually hunting predators, such as birds, are deceived into attacking the hind wing area rather than the true head of the butterfly. In the laboratory, six groups of artificially marked dead cabbage butterflies, Pieris rapae, were presented to Blue Jays, Cyanocitta cristata. Of the six "false head" markings, only the eyespot significantly influenced the point of attack. All of the "false head" markings, however, led to a greater proportion of attacks to the hind wing area of the butterfly. In the course of prey handling following an initial attack, each of the six "false head" markings significantly directed predator handling strikes away from the true head of captive butterflies to the anal angle of the hind wing. In a second experiment, live P. rapae with "false head" markings were mishandled and thus escaped, significantly more frequently than controls. Therefore, "false head" markings may confer a selective advantage by increasing the probability of escape, particularly during handling.


[From the letters (to Freud) to the diary (of Ferenczi)].
This article presents the figures of Sigmund Freud and of Sándor Ferenczi as they appear in their exchange of correspondence, in the close interweaving of their private and professional lives. The most critical aspects of the practice of psychoanalysis, which was the passion and constant preoccupation of the two correspondents, are sounded in this correspondence which also shows the relentless effort that was made by the two men to consolidate the theoretical basis of the field. The document that follows this correspondence, Ferenczi's "Clinical diary" thus appears as an act of self-assertion, being addressed to Freud in a manner no longer explicit but implicit.


Exocrine pancreatic function in Sjögren's syndrome.
Pancreatic function testing was carried out in 19 patients with Sjögren's syndrome (SS) (nine primary type, ten secondary) by the N-benzoyl-tyrosil-p-aminobenzoic acid (PABA) test, serum immunoreactive trypsin (IRT) levels, and stool fat measurements to evaluate the incidence and type of exocrine pancreatic alterations in this disease. Exocrine pancreatic impairment was found to be present in 63% of the patients. Three types of secretory patterns were observed: (1) normal PABA test results and normal IRT levels (37% [7/19] of the patients); (2) normal PABA test results and elevated IRT levels (42% [8/19]; and (3) low PABA test results and elevated IRT levels (21% [4/19]), including two patients with steatorrhea. Functional pancreatic impairment tended to be more severe in patients with longer disease duration and it was related to the degree of alteration of salivary flow but not to labial salivary gland histologic changes or the type of SS. Inasmuch as hypertrypsinemia was the common marker of pancreatic dysfunction in all patients, we suggest a periodic measurement of serum IRT levels in the follow-up of patients with SS to detect early stages of pancreatic involvement.


Call for a Computer-Aided Cancer Detection and Classification Research Initiative in Oman.
Cancer is a major health problem in Oman. It is reported that cancer incidence in Oman is the second highest after Saudi Arabia among Gulf Cooperation Council countries. Based on GLOBOCAN estimates, Oman is predicted to face an almost two-fold increase in cancer incidence in the period 2008-2020. However, cancer research in Oman is still in its infancy. This is due to the fact that medical institutions and infrastructure that play central roles in data collection and analysis are relatively new developments in Oman. We believe the country requires an organized plan and efforts to promote local cancer research. In this paper, we discuss current research progress in cancer diagnosis using machine learning techniques to optimize computer aided cancer detection and classification (CAD). We specifically discuss CAD using two major medical data, i.e., medical imaging and microarray gene expression profiling, because medical imaging like mammography, MRI, and PET have been widely used in Oman for assisting radiologists in early cancer diagnosis and microarray data have been proven to be a reliable source for differential diagnosis. We also discuss future cancer research directions and benefits to Oman economy for entering the cancer research and treatment business as it is a multi-billion dollar industry worldwide.


Multiloculated Cystic Renal Tumors of Childhood: Has the Final Word Been Spoken.
Multicystic renal tumors which include cystic nephroma, cystic partially differentiated nephroblastoma (CPDN) and cystic Wilms tumor has been a diagnostic and therapeutic challenge. Histopathological examination has been the only reliable differentiating method. Management of these tumors is still riddled with controversy as a definitive preoperative differentiation between the three has not been possible. A retrospective evaluation was performed of the treatment strategies employed with nine cases of multicystic renal tumors treated from 2005 to 2015. The median age at presentation was 12 months with all except one being boys. All except two children underwent primary surgery. The median follow-up was 50 months with six children having long-term survival. One child succumbed to the disease process, one died due to an unrelated cause and another was lost to follow-up. Although there was no ambiguity with cases of cystic nephroma (CN) and cystic Wilms tumor, three of the four cases of CPDN had problems. Primary surgery for multicystic renal tumors is safe and should be seriously considered as it prevents overtreatment in cases of CN and early stage CPDN. Further studies are needed to fully understand the biological behavior of CPDN.


Effect of clonazepam and clonidine on primary sleep bruxism: a double-blind, crossover, placebo-controlled trial.
The aim of this study was to assess the acute effects of clonazepam and clonidine on rhythmic masticatory muscle activity in young adults with primary sleep bruxism, as well as accompanying effects on sleep architecture and cardiac activity. This study used a double-blind, crossover, placebo-controlled design. Polysomnography was performed on 19 subjects [nine men and 10 women; mean age (±SE): 25.4 ± 2.7 years] for 5 nights. The first 2 nights were used for the habituation and diagnosis of sleep bruxism. The other 3 nights were randomly assigned for clonazepam (1.0 mg), clonidine (0.15 mg) or placebo (all administered 30 min before bedtime). Sleep, oromotor activity and cardiac activity variables were assessed and compared among the three drug conditions. Clonidine significantly reduced the median percentage of time spent in the rapid eye movement sleep stage compared with placebo and clonazepam. The number of rhythmic masticatory muscle activity episodes was reduced with clonidine by >30% compared with placebo and clonazepam. The reduction of rhythmic masticatory muscle activity index by clonidine was associated with an increase of mean RR intervals (slower heart rate) during quiet sleep periods and during a 70-s period before the onset of rhythmic masticatory muscle activity episodes. However, no changes in cardiac activity variables were observed for clonazepam. In young adults with primary sleep bruxism, clonidine was significantly more effective in suppressing sleep bruxism than clonazepam. The acute effects of clonidine on rhythmic masticatory muscle activity episodes may be mediated by suppression of autonomic nervous system activity and non-rapid eye movement-rapid eye movement sleep processes.


Intravenous loading of valproate for epilepsy.
Valproate is an antiepileptic drug that has broad spectrum activity against several types of seizure. Little information is available about the use of valproate for acute loading of patients when a rapid increase in serum level is needed. We describe the use of intravenous valproate in 20 adults with epilepsy. In each case, a loading dose was calculated by multiplying the patient's body mass, desired change in serum level, and estimated volume of distribution. The mean dose (+/- SD) administered was 1420 +/- 440 mg (19.4 +/- 5.4 mg/kg). In four patients, the dose was infused at 20 mg/min; in all other patients, infusions were performed at 50 mg/min. The infusions were tolerated well and few clinical side effects were observed. Postinfusion levels were drawn and the apparent volume of distribution was calculated to be 0.22 +/- 0.04 L/kg. The results indicate that intravenous valproate may be used to quickly and efficiently increase serum levels in patients with epilepsy.


The teachings of the Tegni in Italian universities in the second half of the fourteenth century.
To challenge the opinion that in the second half of the fourteenth century there was a gap in the production of scholastic exegetical works, this paper discusses nine commentaries on the Tegni that were produced in Padua, Perugia and Bologna and transmitted mostly in the form of recollectiones by students. Their authors were Giovanni Dondi dall'Orologio, Albertino Rinaldi da Salso, Giovanni Santasofia, Antonio da Scarperia, Cristoforo Degli Onesti, Marsilio Santasofia, and the author of Vatican Lat. MS 4472. The interpretation of the Galenic latitudo sanitatis was of central importance in these commentaries and was the focal point for two brief introductions to the first book of the Tegni, written by Bolognino and Pietro d'Arezzo. Bolognino's text is edited in an appendix to this paper.


Early childhood caries: analysis of psychosocial and biological factors in a high-risk population.
The influences that link social factors and caries development are not well understood, although mediation by stress has been suggested. The association between caregiver stress and early childhood caries (ECC), in particular, remains unclear. The purpose of this study was to examine the relationships between parenting stress and ECC while controlling for behavioral and biological factors in a high-risk population. One hundred and fifty healthy children aged 18-36 months were examined in a cross-sectional study design. Parental interviews were conducted to obtain demographic, oral health behavior and parenting stress data. Clinical data included parent and child bacterial measures, fingernail fluoride analyses, caries prevalence and presence of child enamel hypoplasia. Bivariate analyses revealed that parenting stress predicted caries. Multivariate analyses demonstrated that a combination of psychosocial, behavioral, temporal and biological variables predicted ECC outcomes. Total parenting stress did not contribute independently to the best prediction model. Our findings suggest the need for the development of a multidimensional stress model that considers the parent-child dyad to elucidate further the link between psychosocial factors and ECC.


The Use of Multistate Models to Examine Associations of Stress and Adherence With Transitions Among HIV Care States Observed in a Clinical HIV Cohort.
The "cascade of care" is a framework for quantifying the trajectory of people with HIV along the continuum of HIV care. We extended this framework to recognize that individuals may transition back and forth between states of care and to identify factors associated with movement among states of care over time, with particular focus on stress, depression, and adherence. The Ontario HIV Treatment Network Cohort Study is a multisite HIV clinical cohort. We analyzed data from participants who had initiated antiretroviral therapy, achieved virologic suppression, completed ≥1 study questionnaire including psychosocial data, and had ≥1 viral load (VL) result within 2 years of a questionnaire. Follow-up time from the first suppressed VL was divided into 6-month intervals and classified into 1 of 3 states for HIV care retention: (1) suppressed VL (VL <50 copies/mL), (2) unsuppressed VL (VL >50 copies/mL), and (3) unobserved. Multistate models were used to determine the association of transitioning between states and time-updated demographic and clinical characteristics. In total, 1842 participants were included. After multivariable adjustment, poor adherence [hazard ratio (HR) 1.88, 95% confidence interval (CI): 1.19 to 2.98) and stress (HR = 1.38; 95% CI: 1.04 to 1.83) were associated with transitions from suppressed to unsuppressed VL. Similarly, low adherence (HR = 1.52; 95% CI: 1.14 to 2.04) and stress (HR = 1.25; 95%: 1.03, 1.51) were associated with transitions from suppressed to unobserved states. Higher levels of stress and low adherence are associated with transitions to less favorable states of care. Interventions to manage stress and facilitate adherence may improve engagement in HIV care.


Bed-ridden elderly in Japan: social progress and care for the elderly.
The demand for health care and social welfare services for the elderly has increased and in Japan, there is a need in the social system to improve the quality of life, especially for those who are disabled. This article directs attention to bed-ridden elderly persons from the standpoint of social problems attending economic development and population changes based on data from Japan, the United States, Sweden, and OECD countries. Compared to the United States, there are more bed-ridden elderly in Japan, and inadequate public resources for caring. Physicians, nurses, care workers, and rehabilitation specialists such as physiotherapist and occupational therapist per 1000 aged sixty-five or over are 89.5 in Japan while 237.4 in Sweden. Japan has the fewest such health and welfare personnel among developed countries. Even with increases in such personnel through the New Gold Plan, future increase in aged population would off-set the effect and the problem of providing care for the elderly remains.


Five-Loop Running of the QCD Coupling Constant.
We analytically compute the five-loop term in the beta function which governs the running of α_{s}-the quark-gluon coupling constant in QCD. The new term leads to a reduction of the theory uncertainty in α_{s} taken at the Z-boson scale as extracted from the τ-lepton decays as well as to new, improved by one more order of perturbation theory, predictions for the effective coupling constants of the standard model Higgs boson to gluons and for its total decay rate to the quark-antiquark pairs.


Self-organization of memory activity through spike-timing-dependent plasticity.
We studied the self-organization of memory-related activity through spike-timing-dependent plasticity (STDP). Relatively short time windows (approximately 10 ms) for the plasticity rule give rise to asynchronous persistent activity of low rates (20-30 Hz), which is typically observed in delay periods of working memory task. We demonstrate some network level effects on the activity regulation that cannot be addressed in single-neuron studies. For longer time windows (approximately 20 ms), the layered cell assemblies that propagate synchronized spikes (synfire chain) are self-organized. Synchronous spike propagation was suggested to underlie the precisely timed spikes in the monkey prefrontal cortex. The present results suggest that the two networks for sustained activity are different realizations of the same principle for synaptic wiring.


Localization of acetylated alpha-tubulin in Tritrichomonas foetus and Trichomonas vaginalis.
We used monoclonal antibodies specific for acetylated and nonacetylated alpha-tubulin to detect and to localize microtubules containing acetylated alpha-tubulin (stable microtubules) in the pathogenic protozoa Tritrichomonas foetus and Trichomonas vaginalis. SDS-PAGE analysis showed that tubulin is a major protein of both parasites, being enriched in cytoskeletal preparations of whole cells extracted with Triton X-100. The monoclonal antibodies, which recognize all isoforms of alpha-tubulin (B-5-1-2) and only acetylated alpha-tubulin (6-11B-1), bind to the tubulin of T. foetus and T. vaginalis as seen by immunoblotting. Tubulin-containing structures were localized using immunofluorescence microscopy and transmission electron microscopy of the whole cytoskeleton previously incubated in the presence of the anti-tubulin antibodies and a second antibody-gold complex, and then processed using the negative staining or replica techniques. The results obtained indicate that, in addition to the flagellar microtubules, those which form the peltar-axostyle system represent stable microtubules containing acetylated alpha-tubulin.


UiO-66: An Advanced Platform for Investigating the Influence of Functionalization in the Adsorption Removal of Pharmaceutical Waste.
Highly efficient and selective removal of pharmaceuticals and personal care products (PPCPs) from wastewater is a great challenge and is significant. In this study, we chose UiO-66-R, which contains eight isostructural metal-organic frameworks (MOFs) with variable functional groups (-R), as a platform for systemically investigating the influence of functionalization on its adsorption behavior with respect to three classic PPCPs. We conducted kinetic, modeling, and structure-function relationship studies on PPCP removal using MOFs. The adsorption kinetics, including the adsorption rate, affinity, and separation factor ( RL), were comprehensively analyzed and simulated. The design and function of MOFs can greatly promote their adsorption capacity and the efficiency of PPCPs. The structure-function relationship study revealed that hydrogen bonding, electrostatic, and π-π interactions between MOFs and PPCP molecules played important roles in the adsorption process and significantly influenced the adsorption efficiency. This study paves a new way for the application of MOFs with respect to the removal of PPCP pollution and provides guidance for the design of new porous materials for environmental treatment and separation applications.


A test of face discrimination ability in aging and vision loss.
The ability to recognize faces is fundamental to social interactions but has not been studied extensively in visual disorders such as age-related macular degeneration (AMD). We report here the development of a face discrimination test, in which both response times (RTs) and accuracies are measured. Results are compared for young and older control subjects and older adults with AMD to determine the factors underlying performance on this test. Subjects were 14 older controls, 11 young adult controls, and 34 individuals with binocular AMD. In the face discrimination test, colored reference photographs of eight people were presented continuously (male faces in the first half of the test, female faces in the second). On each trial, subjects reported which reference face matched the test face (shown with different poses and/or expressions). In addition, the older controls then identified the expression on the test face. The older controls showed generally small numbers of errors (0 to 9%) on the face identifications but more errors on expression identifications (up to 22%). They tended to show shorter RTs (but no changes in accuracy) with repeated presentations of the same face. The young controls responded more quickly, and they made almost no mistakes. Although performance varied, as a group, those with AMD were slower and showed more errors in identification than the older controls did. Across all subjects, both visual acuity and contrast sensitivity contributed significantly to the variances in RTs and accuracy. The group of older controls had poorer and more variable RTs and accuracies than the young controls. Difficulties in face matching, in terms of both accuracy and RT, were observed for subjects with AMD. Performance accuracy and RTs for this new test depended on both visual acuity and contrast sensitivity.


Longitudinal assessment of airway responsiveness from 1 month to 18 years in the PIAF birth cohort.
The Perth Infant Asthma Follow-up (PIAF) study involves a birth cohort of unselected subjects who have undergone longitudinal assessments of airway responsiveness at 1, 6 and 12 months and 6, 11 and 18 years of age. The aim of this study was to determine the relationship between increased airway responsiveness throughout childhood and asthma in early adult life.Airway responsiveness to histamine, assessed as a dose-response slope (DRS), and a respiratory questionnaire were completed at 1, 6 and 12 months and 6, 11 and 18 years of age.253 children were initially recruited and studied. Airway responsiveness was assessed in 203, 174, 147, 103, 176 and 137 children at the above-mentioned time points, respectively (39 participants being assessed on all test occasions). Asthma at 18 years was associated with increased airway responsiveness at 6, 12 and 18 years, but not during infancy (slope 0.24, 95% CI 0.06-0.42; p=0.01; slope 0.25, 95% CI 0.08-0.49; p=0.006; and slope 0.56, 95% CI 0.29-0.83; p<0.001, respectively).Increased airway responsiveness and its association with asthma at age 18 years is established between infancy and 6 years. We propose that airway responsiveness in early life reflects the initial airway geometry and airway responsiveness later in childhood increasingly reflects immunological responses to environmental influences.


Seasonal environmental changes regulate the expression of the histone variant macroH2A in an eurythermal fish.
Adaptation to cold and warm conditions requires dramatic change in gene expression. The acclimatization process of the common carp Cyprinus carpio L. in its natural habitat has been used to study how organisms respond to natural environmental changes. At the cellular level, adaptation to cold condition is accompanied by a dramatic alteration in nucleolar structure and a down regulation of the expression of ribosomal genes. We show that the enrichment of condensed chromatin in winter adapted cells is not correlated with an increase of the heterochromatin marker trimethyl and monomethyl K20H4. However, the expression of the tri methyl K4 H3 and of the variant histone macroH2A is significantly increased during the winter season together with a hypermethylation of CpG residues. Taking into account the properties of macroH2A toward chromatin structure and dynamics and its role in gene repression our data suggest that the increased expression of macroH2A and the hypermethylation of DNA which occurs upon winter-acclimatization plays a major role for the reorganization of chromatin structure and the regulation of gene expression during the physiological adaptation to a colder environment.


[Protective effects of Sini decoction on adriamycin-induced heart failure and its mechanism: role of superoxide dismutase].
To investigate the role of superoxide dismutase (SOD) in Adriamycin (ADR)-induced heart failure and the protective effects of Sini decoction (SND). SD rats were randomly divided into three groups, control group, heart failure group and SND group. ADR was injected in the rats of heart failure group and SND group by caudal vein. After injection, the rats in SND group were given SND (3.75 g x kg(-1) x d(-1), p.o.). Three weeks later, cardiac function, content of malondialdehyde (MDA) of both myocardium and mitochondria and activity of Cu-Zn SOD and Mn SOD were measured. The mRNA expression of Cu-Zn SOD and Mn SOD were also detected by RT-PCR. Compared with control group, LVSP and +/- dp/dt max were obviously decreased, while LVEDP was markedly increased in the heart failure group. The mRNA expression and the activity of Cu-Zn SOD and Mn SOD in heart failure group were obviously lower than that in the controls'. In addition, the MDA content of both myocardium and mitochondria were clearly increased in heart failure rats. In SND-treated rats, the cardiac function, the activity and the mRNA expression of Cu-Zn SOD and Mn SOD were significantly elevated and the content of MDA was reduced, which had no statistic difference with the rats in control group. The data suggest that oxidative stress is present in the mitochondria of myocardium in ADR-induced heart failure rats and it can be eased by SND. The mechanism may be closely related to SOD.


[Frequency of subclinical hypothyroidism among healthy children and those with neurological conditions in the state of Mérida, Venezuela].
The purpose of this study was to investigate and to compare the frequency and possible aetiology of subclinical hypothyroidism (SH) in healthy and sick children developing neurological disorder changes. One hundred and eighty-seven male and female children between 1 month and 4 years old, 64 with and 123 without neurological disorders, were studied in the state of Mérida, Venezuela. Serum levels of thyrotropin (TSH), free thyroxine (FT4) and urinary iodine were measured by immunofluorescence and by the Sandell-Koltoff's method. Children were diagnosed as having SH if they had high levels of TSH and normal levels of FT4. Antithyroglobulin and antiperoxidase antibodies were measured in children with SH. To establish the frequency of SH, the TSH reference levels on the commercial kit (> 3.8 uU/mL) and the TSH reference levels of our group of healthy children were used. The latter was calculated (X + 2SD) from the values of TSH in the 123 healthy children (> 4.98 uU/mL). The frequency of SH in all children was of 15% when the TSH level from the commercial kit was used and of 6.4% when it was of our group of children (p < 0.001). The frequency of SH value was of 17.2% in children with neurological disorders and of 13.8% in healthy children when the commercial kit's TSH level was used. The frequency of SH in children with neurological disorders was of 7.8% and of 5.7% in healthy children, according to our TSH reference level. This difference was not statistically significant. No significant differences were found in the urinary iodine levels or in the presence of thyroid autoantibodies among the two groups of children with or without SH. There was no association between iodine urinary levels, presence of SH and neurological disorders. We conclude that: 1. In order to make suitable SH level diagnosis in children, we must establish our own levels of reference for TSH. 2. The frequency of SH in children from Mérida state is high, being slightly higher in children with neurological disorders. 3. The aetiology of SH is not due to iodine deficiency or immunological factors.


[Synthesis and characterization of biomacromolecular conjugates for magnetic resonance imaging].
A two-step synthesis method was used to synthesize a series of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-Proxyl conjugates as a contrast agent for magnetic resonance imaging (MRI) of solid tumors. The conjugates were characterized by Proxyl content using UV spectroscopy, electron spin resonance (ESR) spectroscopy and size-exclusion chromatography profile using a Fast Protein Liquid Chromatography instrument. The results show that a series of HPMA copolymer-Proxyl conjugates with incremental increase in Proxyl content were successfully synthesized and characterized, coupled with the macromolecular nature of the conjugates indicate that the copolymers have potential in MRI of solid tumors by enhanced permeability and retention effect.


Effect of Health Education on the Knowledge of Cervical Cancer and Uptake of Papanicolaou Smear Test among Teachers in Uyo, Akwa Ibom State Nigeria: An Interventional Study.
Evidence exists that the uptake of cervical cancer screening is low in Nigeria despite the availability of effective tools. This study determined the effect of health education on the knowledge of cervical cancer and uptake of Papanicolaou (Pap) smear test among teachers in public secondary schools in Uyo, Nigeria. This was an interventional study among public secondary school teachers in Uyo, Akwa Ibom State, Nigeria. It entailed a baseline survey, administration of health education sessions on cervical cancer and its screening tests to the intervention group and a post-intervention evaluation. Data was captured using a semi-structured questionnaire and analyzed with Stata software Version 10. There were 185 respondents each in the interventional and control groups. The mean ages of the teachers were 38.7 ± 8.1 years and 37.1 ± 7.7 years respectively. Post-intervention, knowledge of cervical cancer symptoms increased from 10.1% to 66.5% in the intervention group compared to an increase from 7.0% to 12.0% in the control group (p< 0.001). Similarly, risk factor knowledge improved from 6.1% to 59.5% in the intervention group compared to 4.9% to 7.2% in the control group (p< 0.001). Also, the uptake of the Pap smear test increased from 11.9% to 22.2% in the intervention group (p = 0.01) compared to an increase from 4.9% to 7.0% in the control group (p=0.379). Health education brought about a significant increase in the knowledge of cervical cancer symptoms/risk factors and uptake of Pap smear test and should therefore, be encouraged among teachers in secondary schools.


Can drawing instruction help students with low visuospatial ability in learning anatomy?
Visuospatial skills are considered important attributes when learning anatomy and there is evidence suggesting that this ability can be improved with training techniques including drawing. The Mental Rotations Test (MRT) has been routinely used to assess visuospatial ability. This study aimed to introduce students to drawing as a learning strategy for anatomy. Undergraduate speech science anatomy students took part in a drawing tutorial (n = 92), completed an MRT test, pre- and post-tutorial tests, and surveys regarding their use and attitudes toward drawing as a study tool. The impact on their examination performance was then assessed. Regardless of MRT score or attitude to drawing, students who participated in the drawing tutorial demonstrated immediate improvement in post-tutorial test scores. Students in the drawing group performed better in most anatomy components of the examination, but the result did not reach statistical significance. There was only a positive correlation between MRT score and one type of anatomy question (non-image-based) and speech physics questions (r = 0.315, p = 0.002). The unexpected finding may relate to the MRT which assesses spatial rather than object visualization skills. Students who liked drawing also performed significantly better in word-based and speech physics questions. It is likely that the style of identification question did not require the mental manipulation ability assessed in the MRT. This study demonstrated that students with lower MRT scores are not outperformed in all aspects of anatomy assessment. The study highlights the importance of a more nuanced understanding of visuospatial skills required in anatomy.


Nutritional influences on enzyme activities in saliva of Asian and African elephants.
Asian and African elephants show morphological adaptations to their ecological niche including the oral cavity. Variety and preferences of forage plants differ between both herbivorous elephant species. Diet can affect salivary enzymes. Asian elephants were shown to have a higher salivary amylase activity than African elephants. Species-specific differences were presumed to be influenced by feeding during collection procedure. This study aimed to determine the influence of feeding on enzyme activities in saliva of both elephant species to differentiate from species-specific effects. Additionally, season and housing conditions on salivary enzyme activities in non-fed elephants of both species were investigated. Salivary amylase (sAA), lysozyme (sLYS) and peroxidase (sPOD) activity were measured photometrically or fluorometrically. Results of this study reinforce previous observations of higher basic sAA activity in Asian elephants compared to African elephants. Salivary LYS and sPOD activity showed neither species-specific nor housing-specific differences. Independent from season, most elephants of both species revealed a lack of or low sPOD activity. Feeding caused a temporary decrease of sAA, sLYS and sPOD activity in both elephant species kept in four of eight tested zoos. Furthermore, sAA activity in Asian elephants was higher and sLYS activity lower in Spring than in Autumn. This study summarizes that sAA and sLYS are components of Asian and African elephant saliva in an active conformation in contrast to sPOD. Diet varying between season and zoos might influence sAA and sLYS activities primarily in Asian elephants but temporary low effects suggest sufficient buffer capacity of elephant saliva of both species.


Visfatin Triggers Anorexia and Body Weight Loss through Regulating the Inflammatory Response in the Hypothalamic Microglia.
Visfatin is an adipokine that is secreted from adipose tissue, and it is involved in a variety of physiological processes. In particular, visfatin has been implicated in metabolic diseases, such as obesity and type 2 diabetes, which are directly linked to systemic inflammation. However, the potential impacts of visfatin on the hypothalamic control of energy homeostasis, which is involved in microglial inflammation, have not fully been investigated. In this study, we found that treatment with exogenous recombinant visfatin protein led to the activation of the inflammatory response in a microglial cell line. In addition, we observed that central administration of visfatin led to the activation of microglia in the hypothalamus. Finally, we found that visfatin reduced food intake and body weight through activating POMC neurons in association with microglia activation in mice. These findings indicate that elevation of central visfatin levels may be associated with homeostatic feeding behavior in response to metabolic shifts, such as increased adiposity following inflammatory processes in the hypothalamus.


Daily-Life Physical Activity of Healthy Young Adults Associates With Function and Structure of the Hippocampus.
Previous research on Physical Activity (PA) has been highly valuable in elucidating how PA affects the structure and function of the hippocampus in elderly populations that take part in structured interventions. However, how PA affects the hippocampus in younger populations that perform PA during daily-life activities remains poorly understood. In addition, this research has not examined the impact of PA on the internal structure of the hippocampus. Here, we performed a cross-sectional exploration of the way structural and functional aspects of the hippocampus are associated with habitual PA performed during work, leisure time, and sports in the daily lives of healthy young adults (n = 30; 14 female; mean age = 23.9 y.o.; SD = 7.8 y.o.). We assessed PA in these three different contexts through a validated questionnaire. The results show that PA performed during work time correlated with higher subicular volumes. In addition, we found that PA changed functional connectivity (FC) between a location in the middle/posterior hippocampus and regions of the default mode network, and between a location in the anterior hippocampus and regions of the somatomotor network. No statistical effects of PA performed during leisure time and sports were found. The results generalize the impact of PA on younger populations and show how PA performed in daily-life situations correlates with the precise internal structure and functional connectivity of the hippocampus.


Benzothiazole-based fluorophores of donor-pi-acceptor-pi-donor type displaying high two-photon absorption.
A series of novel heterocycle-based dyes with donor-pi-bridge-acceptor-pi-bridge-donor (D-pi-A-pi-D) structural motif, where benzothiazole serves as an electron-withdrawing core, have been designed and synthesized via palladium-catalyzed Sonogashira and Suzuki-type cross-coupling reactions. All the target chromophores show strong one-photon and two-photon excited emission. The maximum two-photon absorption (TPA) cross sections delta(TPA) of the prepared derivatives bearing diphenylamino functionalities occur at wavelengths ranging from 760 to 800 nm and are as large as approximately 900-1100 GM. One- and two-photon absorption characteristics of the title dyes have also been investigated by using density functional theory (DFT) and the structure-property relationships are discussed. The TPA cross sections calculated by means of quadratic response time-dependent DFT using the Coulomb-attenuated CAM-B3LYP functional support the experimentally observed trends within the series, as well as higher delta(TPA) values of the title compounds compared to those of analogous fluorene or carbazole-derived dyes. In contrast, the traditional B3LYP functional was not successful in predicting the observed trend of TPA cross sections for systems with different central cores. In general, structural modification of the pi-bridge composition by replacement of ethynylene (alkyne) with E-ethenylene (alkene) linkages and/or replacement of dialkylamino electron-donating edge substituents by diarylamino ones results in an increase of delta(TPA) values. The combination of large TPA cross sections and high emission quantum yields makes the title benzothiazole-based dyes attractive for applications involving two-photon excited fluorescence (TPEF).


Mesenchymal stem cells derived from human exocrine pancreas express transcription factors implicated in beta-cell development.
Transplantation of in vitro generated islets or insulin-producing cells represents an attractive option to overcome organ shortage. The aim of this study was to isolate, expand, and characterize cells from human exocrine pancreas and analyze their potential to differentiate into beta cells. Fibroblast-like cells growing out of human exocrine tissue were characterized by flow cytometry and by their capacity to differentiate into mesenchymal cell lineages. During cell expansion and after differentiation toward beta cells, expression of transcription factors of endocrine pancreatic progenitors was analyzed by reverse transcription polymerase chain reaction. Cells emerged from 14/18 human pancreatic exocrine fractions and were expanded up to 40 population doublings. These cells displayed surface antigens similar to mesenchymal stem cells from bone marrow. A culture of these cells in adipogenic and chondrogenic differentiation media allowed differentiation into adipocyte- and chondrocyte-like cells. During expansion, cells expressed transcription factors implicated in islet development such as Isl1, Nkx2.2, Nkx6.1, nestin, Ngn3, Pdx1, and NeuroD. Activin A and hepatocyte growth factor induced an expression of insulin, glucagon, and glucokinase. Proliferating cells with characteristics of mesenchymal stem cells and endocrine progenitors were isolated from exocrine tissue. Under specific conditions, these cells expressed little insulin. Human pancreatic exocrine tissue might thus be a source of endocrine cell progenitors.


Improvement of hyperphagia by activation of cerebral I(1)-imidazoline receptors in streptozotocin-induced diabetic mice.
Imidazoline I1-receptors (I1R) are known to regulate blood pressure and rilmenidine, an agonist, is widely used as antihypertensive agent in clinic. However, the role of I1R in feeding behavior is still unclear. In the present study, we used the agonist of I1R to investigate the effect on hyperphagia in streptozotocin (STZ)-induced diabetic mice. Rilmenidine decreased the food intake of STZ-diabetic mice in a dose-dependent manner. The reduction of food intake was abolished by pretreatment with efaroxan at the dose sufficient to block I1R. Intracerebroventricular (icv) administration of rilmenidine into STZ-diabetic mice also significantly reduced hyperphagia, which was reversed by icv administration of efaroxan. In addition, similar results were observed in STZ-diabetic mice, which received chronic treatment with rilmenidine 3 times daily (t.i.d.) for 7 days. Moreover, the hypothalamic neuropeptide Y (NPY) level was reduced by rilmenidine that was also reversed by pretreatment with efaroxan. In conclusion, the obtained results suggest that rilmenidine can decrease food intake in STZ-diabetic mice through an activation of I1R to lower hypothalamic NPY level.


High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability.
Elevated von Willebrand factor (vWF) concentrations are associated with an increased risk of ischemic heart disease. Several factors influence vWF antigen levels and activity, including blood group, genetic variability, acute-phase response, and proteolysis by A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS13), a determinant of proteolytic cleavage of vWF. We assessed how these factors affect the relation between vWF and the occurrence of stroke to understand the underlying mechanism. In a case-control study of 124 first-ever ischemic stroke patients and 125 age- and sex-matched controls, we studied vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the -1793C/G polymorphism in the vWF gene, and C-reactive protein. vWF antigen and activity levels were significantly higher in cases than in controls. The relative risk of ischemic stroke was highest in individuals in the upper quartile of vWF:Ag (odds ratio, 3.2; 95% CI, 1.4 to 7.5) and vWF:RCo (odds ratio, 2.1; 95% CI, 0.9 to 4.8) compared with individuals in the lowest quartiles. In individuals with ADAMTS13 in the lowest quartile, the relative risk of stroke was 1.7 (95% CI, 0.7 to 3.9) compared with the highest quartile. C-reactive protein, ADAMTS13, and genetic variation did not affect the association between vWF and the relative risk of stroke, whereas blood group did affect the association. vWF antigen and activity are associated with the occurrence of acute ischemic stroke. This relation is unaffected by the severity of the acute-phase response or by genetic variation or degradation.


Isolation of Mycoplasma hominis from a brain abscess.
Mycoplasma hominis is a commensal in the genital tract of women and has been associated with urogenital and extragenital infections. However, central nervous system infections with this organism in adults are very rare. Here we describe the recovery of M. hominis from a brain abscess associated with a postpartum infection. Seroconversion to the isolated strain was detected by both a metabolic inhibition test and an immunoblotting assay. This case demonstrates the pathogenic potential of M. hominis and the need for rapid recognition of the organism so that appropriate chemotherapeutic intervention can occur.


Plasma glucose in screening for diabetes and pre-diabetes: how much is too much? Analysis of fasting plasma glucose and oral glucose tolerance test in Sri Lankans.
Fasting plasma glucose (FPG) is the most commonly used screening tool for diabetes in Sri Lanka. Cut-off values from American Diabetes Association recommendations are adopted in the absence of local data. We aimed to establish FPG cut offs for Sri Lankans to screen for diabetes and pre-diabetes. Data on FPG and diabetes/pre-diabetes status were obtained from Sri Lanka Diabetes and Cardiovascular Study (SLDCS), a community based island wide observational study conducted in 2005-6. Sensitivity specificity and area under the ROC curve were calculated for different FPG values. Study included 4014 community dwelling people after excluding people already on treatment for diabetes or pre-diabetes. Mean age was 45.3 (± 15) years and 60.4% were females. FPG cut off of 5.3 mmol/L showed better sensitivity and specificity than 5.6 mmol/L in detecting diabetes (87.8% and 84.4% Vs 80.8% and 92.1%) and pre-diabetes (54.7% and 87.0% Vs 43.8% and 94.2%). A lower FPG cut off of 5.3 mmol/L has a better sensitivity and acceptable specificity in screening for diabetes and pre-diabetes in Sri Lankan adults.


Isolation of 4-aminopyridine resistant mutants affecting alkali-insoluble glucan content of cell walls in Saccharomyces cerevisiae.
Saccharomyces cerevisiae cells when grown on synthetic medium plates containing 10 mM of 4-aminopyridine (4-AP) undergo cell lysis. Using an ethylmethane sulfonate mutagenesis (EMS) screen, 4-AP resistant mutants (apr) were isolated which could grow on inhibitory concentration of 4-AP. Eighty mutants were obtained that were recessive, monogenic and formed two complementation groups. To identify genes, whose products might be interacting with the apr loci, extragenic suppressors were isolated, which reverted 4-AP resistance phenotype of apr mutants. The suppressors, when genetically characterized, were found to be recessive and represented two loci with overlapping functions. Representative alleles from apr mutants were analyzed for cell wall composition. They were found to have a higher amount of alkali-insoluble glucan signifying the role of alkali-insoluble glucan in cell wall maintenance.


Sensory properties of thickened tomato soup enhanced with different sources of protein (whey, soy, hemp, and pea).
Thickened soup formulations were created with different proteins (hemp, soy, pea, and whey) to improve protein and fluid intake. The formulations consisted of a control soup, and soups with 6% whey protein, 6% hemp protein, 6% pea protein, and 6% soy protein by volume. The suitability of the samples for those living with dysphagia was evaluated using the international dysphagia diet standardization initiative (IDDSI) spoon tilt test and a sensory trial (51 older adults and 51 younger adults). The sensory trial used nine-point hedonic scales and check-all-that-apply to evaluate the different formulations. The sample with the whey addition was not significantly different than the control in terms of liking of flavor and texture, but it decreased the participants' overall liking. The hemp, pea, and soy decreased overall liking as well as liking of flavor and texture. They were associated with off-flavors, aftertaste, and astringency. The responses from the older and younger adults were compared and significant differences were found in their liking of the texture, with the older adults finding the formulations' texture significantly more acceptable. Overall, the study identified that hemp, pea, and soy did not create acceptable thickened soup formulations and the hemp and pea formulations did not achieve a consistency level that is acceptable for those living with dysphagia.


Oxygen therapy for cystic fibrosis.
The most serious complications of cystic fibrosis (CF) relate to respiratory insufficiency. Oxygen supplementation therapy has been a standard of care for individuals with chronic lung diseases associated with hypoxemia for decades. It is common for physicians to prescribe oxygen therapy for people with CF when hypoxemia occurs. However, it is unclear if empiric evidence is available to provide indications for this therapy with its financial costs and often profound impact on lifestyle. To assess whether oxygen therapy improves the longevity or quality of life of individuals with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search of Group's Trials Register: April 2005. Randomized or quasi-randomized controlled trials comparing oxygen, administered at any concentration, by any route, in people with documented CF for any time period. Two authors independently assessed study quality and extracted data. Nine published studies (149 participants) are included in this review, of which only one examined long-term oxygen therapy (28 participants). There was no statistically significant improvement in survival, lung, or cardiac health. Four studies examined the effect of oxygen supplementation during sleep by polysomnography. Although oxygenation improved, there were no demonstrable improvements in qualitative sleep parameters and modest hypoventilation was noted. In three studies, oxygen supplementation was evaluated during exercise. Hypoxemia was prevented, but mild hypercapnia resulted. Work performance was not improved, as measured in one study, but was improved in a second study. Furthermore, in two studies, exercise duration was enhanced by oxygen supplementation. In the study examining the impact of oxygen supplementation after exercise, recovery time was enhanced. There are no published data to guide the prescription of chronic oxygen supplementation to people with advanced lung disease due to CF. Short-term oxygen therapy during sleep and exercise improves oxygenation but is associated with modest and probably clinically inconsequential hypercapnia. During exercise, there are improvements in exercise duration and peak performance. There is a need for larger, well-designed clinical trials to assess the benefits of long-term oxygen therapy in people with CF administered continuously or during exercise or sleep or both.


The Interactions Between Candida albicans and Mucosal Immunity.
Mucosa protects the body against external pathogen invasion. However, pathogen colonies on the mucosa can invade the mucosa when the immunosurveillance is compromised, causing mucosal infection and subsequent diseases. Therefore, it is necessary to timely and effectively monitor and control pathogenic microorganisms through mucosal immunity. Candida albicans is the most prevalent fungi on the mucosa. The C. albicans colonies proliferate and increase their virulence, causing severe infectious diseases and even death, especially in immunocompromised patients. The normal host mucosal immune defense inhibits pathogenic C. albicans through stepwise processes, such as pathogen recognition, cytokine production, and immune cell phagocytosis. Herein, the current advances in the interactions between C. albicans and host mucosal immune defenses have been summarized to improve understanding on the immune mechanisms against fungal infections.


Periostin in Mature Stage Localized Scleroderma.
Periostin is a novel matricellular protein expressed in many tissues, including bone, periodontal ligament, and skin. Although its expression is prominent in various fibrotic conditions, studies of periostin in localized scleroderma are rare. To investigate the expression of periostin and other molecules in localized scleroderma. A retrospective study of 14 patients with confirmed mature stage localized scleroderma was undertaken. Fourteen age-matched and biopsy site-matched subjects with normal skin were included as controls. Collagen fiber deposition, periostin, procollagen, transforming growth factor-β, and matrix metalloproteinase (MMP)-1 expression were assessed and compared between the two groups. Co-localization of α-smooth muscle actin and periostin was evaluated using confocal microscopy. Periostin was predominantly expressed along the dermo-epidermal junction in the controls. Conversely, patients with localized scleroderma demonstrated increased collagen fiber deposition and periostin expression that was more widely distributed along the entire dermis. MMP-1 staining showed increased expression in the epidermis and dermis of patients compared to scanty expression in the controls. A semi-quantitative evaluation showed a higher proportion of excessive collagen bundle deposition (57.1% vs. 7.1%, p=0.013), diffuse periostin positivity (42.9% vs. 0%, p=0.016), and moderate MMP-1 positivity (71.4% vs. 7.1%, p=0.001) in patients than in the controls. Compared to the controls, patients with localized scleroderma had enhanced periostin expression corresponding to increased collagen fiber deposition and unexpected overexpression of MMP-1. The results of this human in vivo study may implicate the pathogenesis of localized scleroderma.


Current therapy of the patent ductus arteriosus.
The patent ductus arteriosus (PDA) was the first congenital heart lesion to be treated surgically and also the first to be treated with nonsurgical catheter intervention. Surgical ligation and division of the ductus remains the gold standard for consistently achieving complete occlusion. Transaxillary muscle-sparing thoracotomy and video-assisted thoracoscopic ligation, however, have evolved as surgical alternatives with reduced trauma, shorter hospitalization, and excellent cosmetic result but are associated with a significant rate of residual or recurrent duct patency. With aggressive application of critical pathway methods, significant reduction in cost has been achieved for surgical PDA closure. Nonsurgical transcatheter closure nevertheless has gained widespread acceptance, mostly employing detachable or nondetachable stainless steel coils. Coils have superseded the previously popular Rashkind PDA occluder (USCI/Bard, Tewksbury, MA) because of significantly lower cost, less cumbersome handling, smaller delivery catheters, and superior occlusion rates. Various coil implantation techniques and detachment mechanisms have been devised. Large PDAs with smallest diameter greater than 5 mm, however, still are better treated surgically until appropriate devices become available.


Relationship between different subpopulations of circulating CD4+ T lymphocytes and microvascular or systemic oxidative stress in humans.
Different components of the immune system, including innate and adaptive immunity (T effector lymphocytes and T regulatory lymphocytes - TREGs) may be involved in the development of hypertension, vascular injury and inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular oxidative stress. Our objective was to investigate possible relationships between T-lymphocyte subtypes and systemic and microvascular oxidative stress in a population of normotensive subjects and hypertensive patients. In the present study we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. A peripheral blood sample was obtained before surgery for assessment of T lymphocyte subpopulations by flow cytometry and circulating indices of oxidative stress. A significant direct correlation was observed between Th1 lymphocytes and reactive oxygen species (ROS) production (mainly in microvessels). Additionally, significant inverse correlations were observed between ROS and total TREGs, or TREGs subtypes. Significant correlations were detected between circulating indices of oxidative stress/inflammation and indices of microvascular morphology/Th1 and Th17 lymphocytes. In addition, a significant inverse correlation was detected between TREGs in subcutaneous small vessels and C reactive protein. Our data suggest that TREG lymphocytes may be protective against microvascular damage, probably because of their anti-oxidant properties, while Th1-Th17 lymphocytes seem to exert an opposite effect, confirming an involvement of adaptive immune system in microvascular damage.


Self directed learning and continuing medical education.
Self directed learning (SDL) for continuing medical education (CME) is the most effective approach for improving physician performance and patient care outcomes. Self directed learning is an essential basis for CME. However, instructor directed programs--particularly on-site conferences--remain the most popular method for acquiring CME. This article briefly examines the evolution of SDL and its importance in lifelong learning for general practice. The challenge for CME providers is to facilitate SDL while taking general practitioners' views and preferences into consideration.


Direct synthesis of ordered imidazolyl-functionalized mesoporous polymers for efficient chemical fixation of CO2.
Ordered imidazolyl-functionalized mesoporous polymers (IM-MPs) are directly synthesized by an evaporation-induced self-assembly method, which are further functionalized with bromoethane and employed as highly efficient and recyclable catalysts for the cycloaddition of CO2 to epoxides.


Selected mitochondrial genes as species markers of the Arctic Contracaecum osculatum complex.
This study, aimed at testing the hypothesis that some mitochondrial genes can serve as species-specific markers, involved a comparison of the sequence variance of selected mitochondrial DNA genes of the Arctic Contracaecum osculatum species (C. osculatum A, C. osculatum B and C. osculatum C). We compared differences between five complete (ND2, CYTB, ND3, ND4L and ND6) and three partial (CO1, CO3 and ND5) protein-coding genes. The total length of the sequence of each of the 13 specimens was 4830 bp. The sample consisted of C. osculatum L3 larvae collected from Reinhardtius hippoglossoides and Gadus ogac from the Barents Sea and Davis Strait. The K2P distance values between the species ranged within 0.06-0.12, the intraspecific variability (0.01-0.03) proving 3-6 times lower. The lowest interspecific divergence was observed between C. osculatum A and C. osculatum B, whereas the highest intraspecific diversity was typical of C. osculatum C. Among the C. osculatum species studied, the highest nucleotide diversity was recorded in the CYTB, CO3 and ND5 genes. These genes may be useful in species identification of the very closely related Contracaecum sibling species.


Identification of high-risk Brugada syndrome patients by combined analysis of late potential and T-wave amplitude variability on ambulatory electrocardiograms.
Risk stratification is important in the management of Brugada syndrome (BrS). Late potentials (LPs) and T-wave amplitude variability (TAV) in high-resolution ambulatory electrocardiography (ECG) were retrospectively investigated. One hundred and twenty-seven patients diagnosed with BrS on 12-lead ECG were classified into 3 groups: documented ventricular fibrillation (VF)/asystole (n=19), episodes of syncope alone (n=30), and asymptomatic (n=78). Healthy volunteers were enrolled as controls (n=25). In the BrS patients, LPs showed appreciable circadian periodicity; filtered QRS duration (fQRS) and duration of the terminal low-amplitude signal <40 μV (LAS40) increased, whereas root mean square voltage of the terminal 40 ms of the fQRS (RMS40) decreased at night compared with the day. TAV did not have such a circadian periodicity. LP-positive incidence (night-time) and peak TAV were as follows: VF/asystole>syncope/asymptomatic>control (P<0.001). VF/asystole was discriminated from control at a ratio of 81-84% by night-time LPs (fQRS >116 ms, LAS40 >35 ms, RMS40 <25 μV) or peak TAV (>54 μV); VF/asystole was discriminated from syncope/asymptomatic at a ratio of 60-69%, by night-time LPs (fQRS >122 ms, LAS40 >42 ms, RMS40 <18μV) or peak TAV (>58 μV). Combined analysis of LPs and peak TAV increased the discriminant ratio up to 93% and 77%, respectively. Analysis of both LPs and TAV (taking circadian periodicity into account) is useful in identification of high-risk BrS patients.


Antigenic composition of a vaccine strain of Francisella tularensis.
The antigenic composition of the live vaccine strain of Francisella tularensis was investigated. Ether-water extracts, water-soluble material from freeze-pressed bacteria and detergent-eluted material from bacterial envelope were allowed to react in immunodiffusion and immunoelectrophoresis with rabbit antiserum against disintegrated bacteria of the vaccine strain. Ten antigenic factors were distinguished in an ether extract. When the extract was precipitated with ammonium sulphate 15 antigenic factors were distinguished in the precipitate and 14 factors in an ethanol precipitate of the supernatant fluid. In the water extract of freeze-pressed material 17 antigenic factors were found. Comparative immunoelectrophoresis of all these fractions demonstrated a minimum of 20 antigenic factors. When envelope material of the vaccine strain was treated with Triton X-100, three more antigenic factors were found to be solubilized. Thus, a total of 23 antigenic factors were distinguished in the extracts. There was a wide variation in heat and trypsin sensitivity between the antigenic factors. A few of the factors had esterase or alkaline phosphatase activity, whereas acid phosphatase, beta-glucuronidase or peroxidase activities were not found in any of the factors.


Targets and candidate agents for type 2 diabetes treatment with computational bioinformatics approach.
We sought to explore the molecular mechanism of type 2 diabetes (T2D) and identify potential drug targets and candidate agents for T2D treatment. The differentially expressed genes (DEGs) were assessed between human pancreatic islets with T2D and normal islets. The dysfunctional pathways, the potential transcription factor, and microRNA targets were analyzed by bioinformatics methods. Moreover, a group of bioactive small molecules were identified based on the connectivity map database. The pathways of Eicosanoid Synthesis, TGF-beta signaling pathway, Prostaglandin Synthesis and Regulation, and Integrated Pancreatic Cancer Pathway were found to be significantly dysregulated in the progression of T2D. The genes of ZADH2 (zinc binding alcohol dehydrogenase domain containing 2), BTBD3 (BTB (POZ) domain containing 3), Cul3-based ligases, LTBP1 (latent-transforming growth factor beta binding protein 1), PDGFRA (alpha-type platelet-derived growth factor receptor), and FST (follistatin) were determined to be significant nodes regulated by potential transcription factors and microRNAs. Besides, two small molecules (sanguinarine and DL-thiorphan) were identified to be capable of reverse T2D. In the present study, a systematic understanding for the mechanism underlying T2D development was provided with biological informatics methods. The significant nodes and bioactive small molecules may be drug targets and candidate agents for T2D treatment.


Safety evaluation of durvalumab for the treatment of non-small-cell lung cancer.
The development of immune checkpoint inhibitors (ICIs), such as anti-programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, has been a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Durvalumab, a PD-L1 inhibitor, has shown survival benefit as a maintenance therapy for patients with unresectable stage III NSCLC following definitive chemoradiotherapy, and is approved by the U.S. Food and Drug Administration and the European Medicines Agency. In this article, we review the development of durvalumab, its pharmacology, and its safety profile as a monotherapy and in combination with other agents, including epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), ICIs such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) blockers, and cytotoxic chemotherapy. ICIs, including durvalumab, cause unique side effects, known as immune-mediated adverse events, which are commonly manageable with standard treatment algorithms. The safety profile of durvalumab monotherapy is similar to those of other PD-1/PD-L1 inhibitors. In the PACIFIC trial, durvalumab after radiotherapy resulted in a slight increase in pulmonary toxicity, but most cases were mild. The enhanced effect of ICIs when used in combination therapies is accompanied by an increased risk of side effects. Therefore, the authors evaluated the safety profile and risk-benefit balance of durvalumab combined with various agents.