Antiapoptotic proteins as targets for bioactive compounds.
One of the most promising strategies in colon cancer therapy is the sensitization of cancer cells to natural proapoptotic cytokines, such as death ligands and interferons, which are able to eliminate abnormal cells. The investigation of mechanisms determining the immune escape of cancer cells revealed the presence of antiapoptotic proteins, such as cFLIP, which inhibit cell death signal transduction. Numerous studies showed that the use of different metabolic inhibitors, such as cycloheximide (CHX), reduces the cFLIP protein level, thus restoring the susceptibility to TNF-alpha-induced apoptosis. However, high non-specific toxicity of CHX excludes the clinical use of this substance. The current efforts are focused on identification of bioactive compounds which could safely support immunotherapy. The review presents in vitro and in vivo evidence that butyrate (Bt), fatty acid produced in colon during fermentation process and parthenolide (PN), sesquiterpene lactone isolated from Tanacetum parthenium specifically affect different cancer cells. Among described various molecular mechanisms of Bt and PN action, one reduces the level of antiapoptotic proteins. This paper clearly demonstrates that bioactive compounds, especially combined with immune cytokines could be seriously considered as an alternative for routine colon anti-cancer therapy.


Intraoperative radiotherapy for locally advanced rectal cancer.
Although intraoperative radiotherapy (IORT) is known to be a method that can reduce local recurrence in locally advanced colorectal cancer, it is not widely used. The aim of this study was to report our experience with IORT for locally advanced rectal cancer. From 1991 to 1994, nine patients with locally advanced rectal cancer received IORT. External beam radiotherapy was given postoperatively in five patients and preoperatively in three. Seven patients received chemotherapy. IORT was done with 6-MeV or 9-MeV electrons, and 12 Gy was irradiated at the tumor bed. The median follow-up period was 84 months (range, 15 to 208 months). The median age of patients was 51 years (range, 42 to 73 years). All patients had advanced clinical T-stage (cT3/4) cancer. The overall and the disease-free survival rates were 66.7% and 66.7% at 5 years, respectively. One patient developed a local recurrence near the anastomosis site, which was out of the IORT field. Four patients died before the last follow-up; three from distant metastasis and one from secondary primary cancer. Adverse effects related to IORT did not occur. Although the number of patients was small in this study, IORT is thought to be safe and effective in reducing local recurrence in locally advanced rectal cancer. However, the role of IORT should be refined in the era of preoperative radio-chemotherapy followed by total mesorectal excision.


Clinical assessment, diagnosis and management of nasal obstruction.
Nasal obstruction is among the most common complaints to the general practitioner (GP). Causes can be divided into mucosal causes or anatomical abnormalities. Most mucosal pathologies can be managed effectively in the primary care setting, with referral to the otolaryngologist in cases that are resistant to medical therapy and in cases of structural anomaly. In cases of allergy, referral to an immunologist may be beneficial. The aim of this article is to review the clinical assessment and management of nasal obstruction in the primary care setting. We consider the various causes of nasal obstruction, describe their management and define those cases that require specialist referral. Nasal obstruction may be acute or chronic and is a manifestation of a wide range of disease processes, most of which are managed by the GP. In patients with persistent nasal obstruction and in those with structural abnormalities, specialist referral is warranted.


Thickness-dependent molecular arrangement and topography of ultrathin ionic liquid films on a silica surface.
The molecular arrangement and topography of ultrathin ionic liquids (ILs) on a silicon wafer have been studied by AFM and ARXPS, respectively. The results indicate a transition from an "anion-cation" layered (smooth) structure to a "drop-on-layer"/"sponge" (rough) structure when the film gets thicker, which can be attributed to the competition between solid/IL attraction and anion-cation cohesion.


Effectiveness of reverse transcription-PCR, virus isolation, and enzyme-linked immunosorbent assay for diagnosis of influenza A virus infection in different age groups.
The degrees of effectiveness of reverse transcription (RT)-PCR, virus isolation, and antigen enzyme-linked immunosorbent assay (ELISA) for the detection of influenza A virus were evaluated with nasopharyngeal swabs from 150 patients (1 week to 86 years old) with influenza A virus infection. RT-PCR had a sensitivity for influenza A virus in stock virus preparations 10(3) times higher than virus isolation and 10(6) to 10(7) times higher than ELISA. The detection rate achieved by RT-PCR in clinical samples was clearly higher (93%) than that by virus isolation (80%) and ELISA (62%). Despite low overall detection rates achieved by antigen ELISA, samples from patients younger than 5 years old yielded higher-than-average rates in this rapid assay (88%). The likelihood of negative results in the ELISA increased significantly with increasing age of the patient (P < 0.01). The degrees of effectiveness of RT-PCR and virus isolation were not influenced by the age of the patient. Neither influenza immunizations nor the interval between onset of symptoms and laboratory investigation (mean, 4.7 days; standard deviation, 3.3 days) affected results obtained by the three test systems. Our results demonstrate that the ELISA is reliable for rapid laboratory diagnosis of influenza in infants and young children, but for older patients application of RT-PCR or virus isolation is necessary to avoid false negative results.


Transient decrease in IL-2-responsive lymphocytes 24 hours after initiation of continuous IL-2 infusion in cancer patients.
Cancer patients were treated with recombinant interleukin-2 (IL-2) in a Phase I clinical trial. Patients were given four repetitive weekly cycles of four days of continuous i.v. IL-2 infusions followed by 3 days of observation. A transient 80% decrease in the number of circulating peripheral blood lymphocytes (PBLs) was noted 24 h after initiation of the IL-2 infusion. The in vitro IL-2 induced proliferative response, and natural killer (NK) activity of the PBLs recovered at this time was only 10-20% of that by the same number of PBLs obtained prior to IL-2 therapy. This effect was transient and rebound increases in circulating lymphocytes expressing high NK and lymphokine-activated killer functions were demonstrated at the end of a 4 day IL-2 infusion. To study further whether the drop in lymphocyte activity observed at initiation of IL-2 therapy was due to activation of a suppressor mechanism, patient PBLs isolated 24 h into the IL-2 infusion were mixed with their pre-IL-2 therapy PBLs at different ratios and assayed in NK and proliferation assays. These mixing experiments did not prove suppression to be the mechanism for the decreased response; rather, the PBLs obtained 24 h into IL-2 therapy merely diluted out the in vitro response of PBLs obtained prior to therapy. Although there was a considerable drop in circulating PBLs 24 h after initiation of each of three subsequent weekly IL-2 treatment cycles, these remaining lymphocytes in the peripheral blood were functional in both NK and IL-2 proliferative assays. These PBLs obtained 24 h into each of the subsequent three cycles showed a progressive increase in their in vitro NK and IL-2-induced proliferative activity, reaching levels two to three times higher than that of pretherapy PBLs by the fourth cycle. Thus, IL-2 caused a transient disappearance of lymphocytes from the circulation at the initiation of each cycle, but lymphocyte function was impaired only in the first IL-2 cycle. These data suggest that resting IL-2 responsive cells initially leave the circulation upon exposure to IL-2, but that such cells become activated and some remain detectable in the circulation when subsequent weekly cycles of IL-2 are given.


Thionamide-induced neutropenia and ecthyma in a pregnant patient with hyperthyroidism.
Agranulocytosis is known to be a rare side effect of thionamides. This complication puts pregnant patients at particular risk for infections. Obstetricians caring for such patients have the difficult task of deciding between conservative or surgical management. The patient is a 37-year-old gravida 4 para 3 Hispanic woman at 11 weeks of gestation with recently diagnosed hyperthyroidism who presented with a neutropenic fever and ecthyma as a complication of thionamide use. She subsequently underwent a thyroidectomy and then had a spontaneous abortion on postoperative day 2. This patient had life-threatening thyrotoxicosis complicated by neutropenic fever and infection, likely caused by a reaction to thionamides. She quickly recovered with broad-spectrum antibiotics. She could not be restarted on methimazole or propylthiouracil as a result of agranulocytosis and thus underwent thyroidectomy.


Expression of beta 2-integrins and L-selectin on polymorphonuclear leukocytes in septic patients.
Adhesion molecules on polymorphonuclear leukocytes (PMNL) play an important role in nonspecific defense mechanisms directed at invading microorganisms. When local infection, however, cannot be controlled, a systemic inflammatory response syndrome (SIRS) ensues which may progress to septic shock and multiple organ failure, these being major determinants of the patient's outcome. In the present study, the expression of beta 2-integrins and L-selectin on blood PMNL was measured on subsequent days in patients with sepsis (n = 17) and in healthy volunteers (n = 15). beta 2-Integrins and L-selectin molecules were detected by flow cytometry, using the monoclonal antibodies IB4 (anti-CD18) and Dreg200 (anti-CD62L), respectively. Adhesion molecules were determined at baseline immediately after blood collection and also 45 min after incubation of cells in vitro at body temperature to allow for spontaneous regulation. In addition, PMNL were activated by receptor-dependent and receptor-independent stimuli to characterize stimulus-specific adhesion molecule expression. In parallel with the measurement of adhesion molecules, severity of sepsis was assessed by the Elebute score. The results demonstrate significant differences in the basal, spontaneous and stimulus-induced expression of adhesion molecules between healthy volunteers, survivors (n = 11) and nonsurvivors (n = 6). Moreover, when survivors and nonsurvivors with severe sepsis (Elebute score > 12) were compared, basal expressions of both beta 2-integrins and L-selectin were significantly lower in patients who did not survive. Thus, measurement of adhesion molecules on circulating PMNL may be useful to identify septic patients at high risk for lethal outcome.


[Identification of serological group 0128:K67 Escherichia].
The authors present the results of studies of etiology of acute group intestinal diseases in neonates from whom escherichia of serological group 0128ac:K67 possessing the following characteristics were isolated: of the same (with the H12 antigen) serological and enzymatic type (nonfermenting sucrose and raffinose, fermenting dulcit and sorbit the first 24 hours, and slowly fermenting ramnose). All the cultures isolated were resistant to the majority of antibiotics used at present, and were only weakly sensitive to erythromycin. Difficulties (agglutination of live cultures with production sera in the absence of low agglutinability of heated cultures) in serological typing of the cultures were due to different partial O-antigen composition of the cultures isolated and of the production strain used in the preparation of commercial sera of the given serological group (0128ab:K67). Because circulation of escherichia of serological 0128ac variant was revealed in the USSR there occurred a necessity of their identification in practical laboratories; for this purpose organization of industrial production of the corresponding serum is necessary.


Office-based anesthesia in Belgium?
For many years, office based anesthesia (OBA), has been considerably increasing in the US. This type of practice is starting to develop in Belgium. On the other side of the atlantic, legislation concerning this practice is becoming more and more precise, whereas the same isn't true in our country. It seems therefore opportune to try and define the different points of view. This article will define the position of the legislator, insurance companies and finally, of the professional organizations. OBA practice is developping insidiously here, and we should therefore ask ourselves serious questions regarding the legal repercussions that it could have. To conclude, we can say that if for a couple of years, the US have started to legislate and propose guidelines, as well as creating special accreditation organizations to inspect and advise the offices, the same is not the case in Belgium. The OBA phenomenon arrived much later here and is really at its very beginnings, but it seems however important to anticipate and clearly regulate this practice in our country.


Experience and results with VV-ECMO for severe acute respiratory failure: weaning versus nonweaning.
Acute respiratory distress syndrome (ARDS) remains an unsolved problem in the intensive care unit (ICU), which can be treated with venovenous extracorporeal membrane oxygenation (VV-ECMO). We summarized retrospectively collected data from an institutional experience with VV-ECMO in patients with severe acute respiratory failure and identified the clinical parameters associated with successful ECMO weaning. Among the 45 cases who received ECMO for pneumonia (n = 19), exacerbation of interstitial lung disease (n = 11), ARDS secondary to sepsis (n = 8), aspiration pneumonitis (n = 2), postoperative ARDS (n = 3), and others (n = 2), 21 (46.7%) were successfully weaned from ECMO. In a univariate analysis median platelet (PLT) count at ICU admission (162 vs. 97 × 10/L; p = 0.046) and pre-day 1 (118.5 vs. 62.5 × 10/L; p = 0.046) was higher in the ECMO-weaned group than those in the weaning failure group. Using a PLT level of 70 × 10/L, the odds ratio for successful ECMO weaning was 11.0 (95% confidence interval [CI] 1.34-87.16; p = 0.023) in the multivariate analysis. Bleeding complication rates were similar between the two groups. High PLT counts at ICU admission and the day immediately before initiating ECMO might play a key role in successful weaning of VV-ECMO for severe acute respiratory failure. Further studies should evaluate the proper target PLT level to enhance ECMO outcomes.


Effect of backleak in nephron dynamics.
The effect of transepithelial solute, i.e., sodium chloride, backleak is taken into consideration in the spatiotemporal evolution of the chloride concentration along the thick ascending limb of a single nephron. The importance of the mechanism and of its mathematical modeling is argued on physiological grounds. The backleak "strength" is found to significantly modify the threshold for the appearance of temporally oscillatory behavior in the chloride concentration in the thick ascending limb which has previously been experimentally observed in normotensive rats.


Synthesis of trans-L/D-2-(tert-butoxycarbonyl-aminomethyl)-4-(thymin-1-yl) pyrrolidin-1-yl acetic acid.
To delineate the binding preferences of stereochemically divergent pyrrolidine PNAs, synthesis of all four diastreomeric monomers of I and the systematic complexation studies of the resultant PNAs with complementary DNA/RNA is essential. We herein report the synthesis of trans-L/D-2-(tert-butoxycarbonyl-aminomethyl)-4-(thymin-1-yl) pyrrolidin-1-yl acetic acids I, their incorporation in PNA oligomers and DNA binding studies will be presented.


Microbial skin flora of selected cancer patients and hospital personnel.
The bacterial flora of the skin from five anatomical sites on 10 leukemia patients, 10 patients with malignant melanoma, and a control group of 10 medical personnel was examined quantitatively and qualitatively. This was done to determine whether malignant disease results in changes in skin flora and to establish carrier rates of gram-negative bacteria on the skin of personnel in hospital environments. Gram-negative bacteria were isolated more frequently (74 isolates from 100 cultures) from the skin of leukemia patients than from either patients with malignant melanoma (8 isolates from 100 cultures) or the medical personnel (9 isolates from 100 cultures). Klebsiella pneumoniae and Pseudomonas aeruginosa were isolated exclusively from leukemia patients. Relative proportions of gram-negative bacteria in total populations were determined. The axilla was the only site with a uniformly high proportion of gram-negative bacteria. From all other sites cultured, gram-negative populations were low (1 to 5 bacteria/cm2 of skin), although a high proportion of gram-negative populations occurred randomly throughout all subject groups. It was concluded that leukemia patients tend to carry gram-negative bacteria on the skin. The factors permitting colonization of skin by gram-negative bacteria are discussed.


Granulocytes impose a tight bottleneck upon the gut luminal pathogen population during Salmonella typhimurium colitis.
Topological, chemical and immunological barriers are thought to limit infection by enteropathogenic bacteria. However, in many cases these barriers and their consequences for the infection process remain incompletely understood. Here, we employed a mouse model for Salmonella colitis and a mixed inoculum approach to identify barriers limiting the gut luminal pathogen population. Mice were infected via the oral route with wild type S. Typhimurium (S. Tm) and/or mixtures of phenotypically identical but differentially tagged S. Tm strains ("WITS", wild-type isogenic tagged strains), which can be individually tracked by quantitative real-time PCR. WITS dilution experiments identified a substantial loss in tag/genetic diversity within the gut luminal S. Tm population by days 2-4 post infection. The diversity-loss was not attributable to overgrowth by S. Tm mutants, but required inflammation, Gr-1+ cells (mainly neutrophilic granulocytes) and most likely NADPH-oxidase-mediated defense, but not iNOS. Mathematical modelling indicated that inflammation inflicts a bottleneck transiently restricting the gut luminal S. Tm population to approximately 6000 cells and plating experiments verified a transient, inflammation- and Gr-1+ cell-dependent dip in the gut luminal S. Tm population at day 2 post infection. We conclude that granulocytes, an important clinical hallmark of S. Tm-induced inflammation, impose a drastic bottleneck upon the pathogen population. This extends the current view of inflammation-fuelled gut-luminal Salmonella growth by establishing the host response in the intestinal lumen as a double-edged sword, fostering and diminishing colonization in a dynamic equilibrium. Our work identifies a potent immune defense against gut infection and reveals a potential Achilles' heel of the infection process which might be targeted for therapy.


Magic trick: a behavioural strategy for the management of strong-willed children.
The purpose of this study was to compare the effectiveness of using a magic trick to persuade strong-willed children who refuse to sit in the dental chair at the first visit with more conventional methods like tell-show-do (TSD). Seventy children aged 3-6 years of age who were identified as manifesting strong-willed behaviour were selected for this study. The children were randomly assigned to be managed either by a magic trick distraction or by TSD. There were 35 subjects in each group. The following variables were recorded for each child: time from the beginning of the session to sitting on the dental chair (in minutes); ability to perform a dental examination (yes or no); and Frankl's behavioural category. Children who were shown a magic trick (Magic+) sat significantly faster on the dental chair than children who were not shown the magic trick (Magic-) (141.2+/-71.5 and 221.7+/-110.7 s, respectively). In addition, radiographs could be taken in significantly more Magic+ children (91% and 54%, respectively). When time till sitting on dental chair, radiographs taken and Frankl's behavioural categories were examined by gender, age, first time at the dentist and by parent assessment, the following pattern emerged: (1) Children in the Magic+ group sat on the dental chair significantly faster than children in the Magic- group. (2) Radiographs could be taken for more Magic+ children. (3) The Magic+ children demonstrated more cooperative behaviour (Frankl's categories 3 and 4). This study demonstrates that a magic trick is able to facilitate two types of cooperative behaviour: (1) it expedites the movement of the child into the dental chair; and (2) it enables the dentist to take radiographs more easily.


Family planning program effects on the fertility of low-income U.S. women.
Under rigorous statistical controls, it has been shown that the larger the proportion of lower SES women enrolled in organized family planning programs, the lower their fertility. Program effects independent of other social, economic and cultural factors were shown for lower SES whites and blacks, and for most age groups. The potential of a fully implemented program to reduce fertility differentials between upper and lower SES groups was assessed, using 1969-1970 fertility rates and the estimates of 1969 program impact. Although we believe that the program's impact has increased in magnitude over time, even these estimates from an early point in U.S. program development provide impressive documentation that the program reduces fertility in the subpopulation served by the program, and, by implication, that there is a genuine need for organized family planning services, even in an industrialized nation like the United States. If there were no need, there could be no program effect. The family planning program was one of the major new health and social programs introduced in the mid-1960s. This study shows that, far from failing, the program was succeeding very well in attaining its objectives. The program works because it gives women of lower socioeconomic status access to modern and effective methods of contraception that they would not otherwise have. As a result, the rates of unwanted and mistimed pregnancy of patients are lower than those of comparable women who lack access to organized clinic programs.


Beyond Reperfusion: Acute Ventricular Unloading and Cardioprotection During Myocardial Infarction.
Heart failure is a major cause of morbidity and mortality around the world, and myocardial infarction is its leading cause. Myocardial infarction destroys viable myocardium, and this dead tissue is replaced by a non-contractile scar that results in impaired cardiac function and a significantly increased likelihood of the patient developing heart failure. Limiting infarct scar size has been the target of pre-clinical and clinical investigations for decades. However, beyond reperfusion, few therapies have translated into the clinic that limit its formation. New approaches are needed. This review will focus on new clinical and pre-clinical data demonstrating that acute ventricular unloading prior to reperfusion by means of percutaneous left ventricular support devices reduces ischemia-reperfusion injury and limits infarct scar size. Emphasis will be given to summarizing our current mechanistic understanding of this new therapeutic approach to treating myocardial infarction.


Hair and Scalp Disorders in a Tuscan Pediatric Dermatological Outpatient Clinic: A Clinical and Epidemiological Evaluation.
The aim of this study was to evaluate the clinical and epidemiological profile of hair and scalp disorders in children referred to the Pediatric Dermatology Outpatient Clinic. We performed a retrospective study of children with hair loss problems or scalp diseases who turned to the Pediatric Dermatology Service, Anna Meyer Pediatric Hospital, Florence, Italy, from January 1, 2009, to December 31, 2009. Demographics, personal and familial medical history, laboratory tests, clinical examination, final diagnosis and therapeutic interventions were obtained from the manual chart review. Of the 2,640 children who had access to the Pediatric Dermatology Service, 190 (7.19%) had a hair or scalp disorder. Among the 190 children, 60 (31.57%) presented with nonscarring alopecia, 56 (29.47%) had benign neoplasias, hamartomas or vascular malformations of the scalp, 51 (26.84%) had scalp inflammatory diseases, 14 (7.36%) had scarring alopecia, 5 (2.63%) had infections and 2 (1.05%) had infestation of the scalp. A case of constitutional hypertrichosis (0.52%) and also a case (0.52%) of lamellar ichthyosis were diagnosed. Our results underline that hair and scalp diseases represent an important percentage of admittances to a dermatological pediatric outpatient clinic. The variety and complexity of the diseases observed in this study included diseases commonly found also in adulthood.


Specificity of antibodies to type II collagen in rheumatoid arthritis.
To reassess the role of autoantibodies to type II collagen in the pathogenesis of diseases, we studied antibodies from patients with rheumatoid arthritis (RA) and from patients with relapsing polychondritis for species specificity and collagen type specificity, using an improved enzyme-linked immunosorbent assay. Antibodies were found in the sera of 15% of the RA patients and 50% of the relapsing polychondritis patients, as well as in the cartilage of 69% of the RA patients examined. Reaction with both homologous and heterologous type II collagens was common. Analysis of 19 selected RA sera revealed that autoantibodies were generally associated with specific antibodies to some species of heterologous type II collagen. In contrast, antibodies found in 4% of the non-RA controls were specific for either bovine or chick type II collagen. These findings indicate that autoantibody formation in RA and relapsing polychondritis may occur as a result of an immune response to heterologous type II collagen. However, since RA and relapsing polychondritis patient sera differed in their reactivity with the cyanogen bromide-digested peptides, it is possible that the clinical manifestation of collagen autoimmunity might be influenced by the epitope specificity of the antibodies.


Positive mental health: a turn of the century perspective.
Within the last decade, a national prevention research, training, and practice agenda on mental health has been established to address the epidemiological increases in mental disorders and associated emotional and financial costs to individuals, families, and communities. In this article, the author reviews theoretical, empirical, and public policy support in favor of prevention science that inherently includes a broad positive mental health orientation with an emphasis on mental health promotion processes. Prevention within the mental health field needs to include not only minimizing mental disorders, but also enhancing positive qualities of daily functioning. The socioeconomic and cultural context of positive mental health is emphasized with particular attention given to the interrelatedness of individual, family, and community "collective sense of well being." Nursing and interdisciplinary contributions are reviewed, noting implications for future public policy and service system changes. Innovative ways to enhance mental health will require study of system integration across primary and mental health services as well as incorporating services within societal institutions such as schools and the workplace.


Automated Camera Lucida Method with Colored Images through Integration of Hardware and Software in Microscopic Zooming.
Automating the camera Lucida method which is a standard way for focusing microscopic images is a very challenging study for many scientists. Hence, actually combining hardware and software to automate microscopic imaging systems is one of the most important issues in the field of medicine as well. This idea reduces scanning time and increases the accuracy of user's results in this field. Closed-loop control system has been designed and implemented in the hardware part to move the stage in predefined limits of 15°. This system produces 50 consecutive images from parasites at the mentioned spatial distances in two directions of the z-axis. Then, by introducing our proposed relational software with combining images, a high-contrast image can be presented. This colored image is focused on many subparts of the sample even with different ruggedness. After implementing the closed-loop controller, stages movement was repeated eight times with an average step displacement of 20 μm which were measured in two directions of the z-axis by a digital micrometer. On average, the movement's error was 1 μm. In software, the edge intensity energy index has been calculated for image quality evaluation. The standard camera Lucida method has been simulated with acceptable results based on experts' opinions and also mean squared error parameters. Mechanical movement in stage has an accuracy of about 95% which will meet the expectations of laboratory user. Although output-focused colored images from our combining software can be replaced by the traditional fully accepted Camera Lucida method.


[T cell leukemia antigens, FT-1 and FT-2].
The understanding of the differentiation process of lymphocytes in the embryonic thymus has been based on extrapolation from adult thymic lymphocytes. The study presented here was mainly concerned with the new cell surface antigens designated FT (FT-1, FT-2), which are expressed on fetal thymocytes of all mouse strains examined, but not on thymocytes or any other lymphoid cells of adult mice. One of the interesting features of FT antigens is the timing of their expression in connection with the ontogeny of thymic lymphocytes. A majority of fetal thymocytes at the 13th day of gestation express FT antigens, whereas no positive cells are found in fetal liver. Therefore, FT antigens seem to appear as soon as the stem cells have reached the thymus. The proportion of FT+ cells then declines sharply with increase in the time of gestation, while Thy-1+ cells increase in inverse proportion. All of these results seem to support the idea that the thymocytes expressing FT antigens are replaced with Thy-1+ thymocytes, although the possibility of the transition from FT+ to Thy-1+ cells cannot be excluded. It was also demonstrated that fetal thymocytes are heterogeneous with respect to the expression of FT-1 and FT-2 antigens. Especially, thymic lymphocytes at the earlier stages of ontogeny can be divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-. With the emergence of Lyt antigens, these subpopulations seem to differentiate and acquire far more complicated features. Such cellular heterogeneity probably reflects the complexed events like selection, deletion or amplification occurring in the embryonic thymus. Another interesting aspect of FT antigens is their reappearance on the surface of thymic leukemia cells. Biochemical studies have indicated that the molecular weight of FT-1 antigen on leukemia cells is about 100,000 by means of biosynthetic labeling with either [3H]-galactose or [35S]-methionine. FT-1 antigen on fetal thymocytes also appeared as a major band with m.w. 100,000. Two-dimensional gel electrophoresis revealed that FT-1 antigenic determinants appear to reside on a family of glycoproteins with extensive charge heterogeneity. All of these results suggest that FT antigens, especially FT-1 antigen, will be useful markers for understanding the mechanism underlying the activation of normally silent genetic information in leukemia cells. In summary, further biochemical and genetic analysis of FT antigens will contribute to an understanding of the ontogenic development of T cells as well as the leukemogenesis of T cell leukemias.


Dispersed Chromosomal Stat5b-binding elements mediate growth hormone-activated insulin-like growth factor-I gene transcription.
The growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis regulates somatic growth during childhood and orchestrates tissue repair throughout the life span. Recently described inactivating mutations in Stat5b in humans with impaired growth have focused attention on this transcription factor as a key agent linking GH-stimulated signals to IGF-I gene expression, and several putative Stat5b sites have been identified in the IGF-I gene. Here, we define and characterize potential GH- and Stat5b-activated chromosomal enhancers that can regulate IGF-I gene transcription. Of 89 recognizable Stat5 sequences in 200 kb centering on the rat IGF-I gene, 22 resided within conserved regions and/or were identical among different species. Only 15 of these sites, organized into 7 distinct domains, were found to bind Stat5b by quantitative chromatin immunoprecipitation assays in liver chromatin of rats, but only after acute GH treatment. These sites could bind Stat5b in vitro, and individual domains could mediate GH- and Stat5b-stimulated IGF-I promoter activity in cultured cells. Further analyses revealed that four Stat5b domains possessed chromatin signatures of enhancers, including binding of co-activators p300 and Med1, and RNA polymerase II. These modifications preceded GH-stimulated recruitment of Stat5b, as did lysine 4 monomethylation of histone H3, which was enriched in 6/7 Stat5b-binding elements. In contrast, histone acetylation was induced by GH but was limited to Stat5b binding domains found within the IGF-I transcription unit. We conclude that GH stimulates recruitment of Stat5b to multiple dispersed regions within the igf1 locus, including several with properties consistent with long range transcriptional enhancers that collectively regulate GH-activated IGF-I gene transcription.


Outlining the Roles of Membrane-Foulant and Foulant-Foulant Interactions in Organic Fouling During Microfiltration and Ultrafiltration: A Mini-Review.
Membrane fouling remains a notorious problem in microfiltration (MF) and ultrafiltration (UF), and a systematic understanding of the fouling mechanisms is fundamental for solving this problem. Given a wide assortment of fouling studies in the literature, it is essential that the numerous pieces of information on this topic could be clearly compiled. In this review, we outline the roles of membrane-foulant and foulant-foulant intermolecular interactions in MF/UF organic fouling. The membrane-foulant interactions govern the initial pore blocking and adsorption stage, whereas the foulant-foulant interactions prevail in the subsequent build-up of a surface foulant layer (e.g., a gel layer). We classify the interactions into non-covalent interactions (e.g., hydrophobic and electrostatic interactions), covalent interactions (e.g., metal-organic complexation), and spatial effects (related to pore structure, surface morphology, and foulants size for instance). They have either short- or long-range influences on the transportation and immobilization of the foulant toward the membrane. Specifically, we profile the individual impacts and interplay between the different interactions along the fouling stages. Finally, anti-fouling strategies are discussed for a targeted control of the membrane-foulant and foulant-foulant interactions.


Variability of the rs333 in Polish patients with lupus erythematosus.
Lupus erythematosus (LE) is an autoimmune disease with a strong influence of genetic and environmental factors. C-C motif chemokine receptor 5 (CCR5) gene expression may affect the development and intensity of LE. To evaluate the possible association between the 32bp deletion in rs333 locus located within the CCR5 gene and the development of LE or the occurrence of various clinical symptoms in the course of the disease. One hundred and twenty patients with LE (77 with systemic lupus erythematosus (SLE) and 43 with discoid lupus erythematosus (DLE)) and 100 healthy controls from the Polish population were genotyped for deletion in rs333. 32 bp deletion in the rs333 was significantly more frequent among healthy individuals than DLE patients. Moreover, heterozygotes and homozygotes with deletion in rs333 were significantly more frequent within the control group than the group of patients with discoid lupus erythematosus. In contrast, any statistically significant differences in allele or genotype frequencies between healthy persons and SLE patients were observed. Furthermore, nucleotide sequence variability of rs333 was not associated with certain clinical symptoms of LE patients. Deletion in the rs333 might be a protective factor for DLE, but not SLE in the Polish population. Nevertheless further studies performed on larger populations are needed to confirm these observations.


[Pathogens and risk factors for ventilator-associated pneumonia in neonates].
To study the pathogens, drug sensitivity and risk factors for ventilator-associated pneumonia (VAP) in neonates. Retrospective analysis was performed on the clinical data of 401 neonates who were admitted to the neonatal intensive care unit and received mechanical ventilation for 48 hours or longer from January 2008 to February 2012. Eighty-five of the 401 neonates suffered VAP. The main pathogens for VAP were Gram-negative bacteria (97%), including Klebsiella pneumoniae (51%), Acinetobacter baumannii (17%) and Escherichia coli (12%) as the three most frequent ones. The drug sensitivity test showed that these pathogens developed resistance to amoxicillin, amoxicillin/clavulanic acid, piperacillin, ceftazidime, cefazolin, and cefotaxime, with a susceptibility rate of below 15%, and demonstrated decreased sensitivity to imipenem and meropenem, with a susceptibility rate of below 75%. The independent risk factors for neonatal VAP included birth weight (OR=1.399, P<0.05), duration of mechanical ventilation (OR=1.966, P<0.01), length of hospital stay (OR=1.812, P<0.01), times of tracheal intubation (OR=2.056, P<0.01), and 1 min Apgar score (OR=2.146, P<0.01). The incidence of neonatal VAP is influenced by many factors. The main pathogens for neonatal VAP are Gram-negative bacteria and antibacterial agents should be properly used according to drug sensitivity test results. Comprehensive prevention and control measures should be taken to reduce the incidence of VAP.


The Impact Of Medicare's Mental Health Cost-Sharing Parity On Use Of Mental Health Care Services.
Before the implementation of cost-sharing parity in Medicare, beneficiaries faced higher cost sharing for mental health services than for other medical services. The Medicare Improvements for Patients and Providers Act of 2008 phased in cost-sharing reductions in Medicare for outpatient mental health services in the period 2010-14. Using data for 2006-15 from the Medical Expenditure Panel Survey and difference-in-differences analyses, we assessed whether this reduction in mental health cost sharing was associated with changes in specialty and primary care outpatient mental health visits and psychotropic medication fills. We compared people with Medicare and with private insurance before and after parity implementation. Medicare beneficiaries' use of psychotropic medication increased after the implementation of cost-sharing parity, but we did not detect a change in visits. Changes in the use of psychotropic medications were greater among people with probable serious mental illness and among Medicare beneficiaries who did not report having supplemental coverage. The increased medication use could signal improvements in mental health care access among Medicare beneficiaries, especially among the subgroups most likely to benefit from the policy change.


Centrobin regulates centrosome function in interphase cells by limiting pericentriolar matrix recruitment.
The amount of pericentriolar matrix at the centrosome is tightly linked to both microtubule nucleation and centriole duplication, although the exact mechanism by which pericentriolar matrix levels are regulated is unclear. Here we show that Centrobin, a centrosomal protein, is involved in regulating these levels. Interphase microtubule arrays in Centrobin-depleted cells are more focused around the centrosome and are less stable than the arrays in control cells. Centrobin-depleted cells initiate microtubule nucleation more rapidly than control cells and exhibit an increase in the number of growing microtubule ends emanating from the centrosome, while the parameters of microtubule plus end dynamics around the centrosome are not significantly altered. Finally, we show that Centrobin depletion results in the increased recruitment of pericentriolar matrix proteins to the centrosome, including γ-tubulin, AKAP450, Kendrin and PCM-1. We propose that Centrobin might regulate microtubule nucleation and organization by controlling the amount of pericentriolar matrix.


Per-oral extended-release bioadhesive tablet formulation of verapamil HCl.
The objective of this study was to formulate a hydrogel-forming bioadhesive drug delivery system for oral administration of verapamil HCl (VP). This system is a non-distintegrating gastro-retentive tablet to allow continuous slow release of VP in the stomach medium where it is more soluble. Different formulate of VP tablets were prepared by compression using various proportions of hydroxypropyl cellulose (HPC) and carbopol 934p (CP). The effect of polymer concentration on the release profile, water uptake and in vitro bioadhesion was studied. Five formulae (F3-F7) exhibited slow release profiles. Formulations F6 (40% HPC and 30% CP) and F7 (40% HPC and 40% CP) had the slowest. They showed 63.6 and 52.2% drug release, respectively, after 12 hours. The kinetic analysis of the release data demonstrated that the bigbest linearity were achieved when data fitted in Higuchi equation rather than zero or first order equations. They had n values close to 0.5 that confirming their Higuchi diffusion. F3 showed the highest swelling index (101.2%), however, the detachment force was intermediate (1.427 N/cm2). Formulae (F4-F7) showed relatively strong in-vitro bioadhesive force. They had detachment forces higher than 1 N/cm2. In general, a delay in drug release and an increase in the in-vitro bioadhesion was seen with the increase in both polymer concentrations. The in vitro data revealed that Formulae F4-F7 served the dual purpose of bioadhesion and sustained release.


Dynamics of permeable particles in concentrated suspensions.
We calculate short-time diffusion properties of suspensions of porous colloidal particles as a function of their permeability, for the full fluid-phase concentration range. The particles are modeled as spheres of uniform permeability with excluded volume interactions. Using a precise multipole method encoded in the HYDROMULTIPOLE program, results are presented for the hydrodynamic function, H(q) , sedimentation coefficient, and self-diffusion coefficients with a full account of many-body hydrodynamic interactions. While self-diffusion and sedimentation are strongly permeability dependent, the wave-number dependence of the hydrodynamic function can be reduced by appropriate shifting and scaling, to a single master curve, independent of permeability. Generic features of the permeable sphere model are discussed.


A Rare Case of Paraneoplastic Syndrome of Inappropriate Secretion of Antidiuretic Hormone in Cervical Squamous Cell Carcinoma; A Case Report and Literature Review.
SIADH is more commonly associated with small cell lung cancer but has also been associated with other malignancies such as oropharyngeal, gastrointestinal, genitourinary, endocrine, lymphomas, and sarcomas. There have been few reports of small cell carcinoma of the cervix complicated by SIADH; however, not many cases are associated with squamous cell carcinoma of the cervix. We present a case of a patient with squamous cell carcinoma of the cervix with a paraneoplastic syndrome of inappropriate secretion of antidiuretic hormone. The pathophysiology, clinical picture, and treatment are also discussed.


Sensitivity of phenotypic susceptibility analyses for nonthymidine nucleoside analogues conferred by K65R or M184V in mixtures with wild-type HIV-1.
Thymidine-sparing triple-nucleoside regimens have exhibited poor virologic response despite apparent phenotypic susceptibility to 2 of 3 regimen components at early time points. Phenotypic resistance masking by wild-type virus may explain this discrepancy.Consistent with this notion were (1) the presence of low level nucleoside reverse-transcriptase inhibitor-resistant human immunodeficiency virus in subjects receiving failing first-line regimens consisting of tenofovir (TDF), abacavir (ABC), and lamivudine (3TC); (2) lower fold resistance associated with mixtures versus mutants in a clinical-isolate database; and (3) dose dependent changes in susceptibility to ABC, 3TC, TDF, and didanosine on titration of K65R and/or M184V with wild-type virus. These findings underscore the limitations of stand-alone phenotypic susceptibility measures and emphasize the importance of complementary and/or more sensitive techniques.


[Fat and fatty acid content in selected powdered ready to eat dishes].
Fat content as well as fatty acids composition in 16 powdered ready to eat dishes from the market in Warsaw area in the year of 2001 has been analysed. We have found, that fat content in these products was from 5.2 to 24.1%. Saturated fatty acids were dominant in the fat derived of these products and also trans isomers unsaturated fatty acids, know from recent finding as having negative nutritional effect.


Simplifying adherence in schizophrenia.
Treatment nonadherence is a formidable challenge in today's clinical practice. Despite decades of focused research, medication adherence continues to be a significant risk factor for poor prognosis in schizophrenia. Studies demonstrate that no single strategy is effective for all patients and that a multidisciplinary approach customized to the patient's individual needs results in improved adherence rates. This Open Forum presents a comprehensive model for organizing and incorporating current and future evidence-based strategies with a focus on educational strategies, psychotherapeutic techniques, and a strong therapeutic alliance.


Delirium in older adults.
Delirium is a common neuropsychiatric syndrome in the elderly that can occur in several different settings caused by several different processes. It is common and causes increased morbidity and mortality to those affected. This clinical review discusses the prediction, prevention, diagnosis, and treatment of delirium in the elderly population. Several strategies to predict delirium are noted with the discussion of pharmacological and nonpharmacological trials of prevention and treatment. Diagnosis of delirium, specifically with the use of objective instruments, is discussed, as is the evidence for pharmacological and nonpharmacological treatment strategies. Discussion of the neurobiology and genetic markers for delirium may elucidate further areas for future research.


Endoscopic screening for varices in cirrhosis: findings, implications, and outcomes.
At least two thirds of cirrhotic patients develop esophageal varices during their lifetime. Severe upper gastrointestinal (UGI) bleeding as a complication of portal hypertension develops in about 30%-40% of cirrhotics. Despite significant improvements in the early diagnosis and treatment of esophagogastric variceal hemorrhage, the mortality rate of first variceal hemorrhage remains high (20%-35%). Primary prophylaxis, the focus of this article, is treatment of patients who never had previous variceal bleeding to prevent the first variceal hemorrhage. The potential of preventing first variceal hemorrhage offers the promise of reducing mortality, morbidity, and associated health care costs. This article (1) reviews endoscopic grading of size and stigmata for esophageal and gastric varices, (2) describes data on prevalence and incidence of esophageal and gastric varices from prospective studies, (3) discusses independent risk factors from multivariate analyses of prospective studies for development of first esophageal or gastric variceal hemorrhage and possible stratification of patients based on these risk factors, (4) comments on the potential cost effectiveness of screening all newly diagnosed cirrhotic patients and treating high-risk patients with medical or endoscopic therapies, and (5) recommends further studies of endoscopic screening, stratification, and outcomes in prospective studies of endoscopic therapy. The author's recommendations are to perform endoscopic screening for the following subgroups of cirrhotics: all newly diagnosed cirrhotic patients and all other cirrhotics who are medically stable, willing to be treated prophylactically, and would benefit from medical or endoscopic therapies. Exclude patients who are unlikely to benefit from prophylactic therapies designed to prevent the first variceal hemorrhage, those with short life expectancy, and those with previous UGI hemorrhage (they should have already undergone endoscopy). For low or very low risk cirrhotic patients-those found to have no varices or small varices without stigmata-repeat endoscopy is recommended because screening for progression may be warranted in 2 or more years.


[Immunological disorders in epileptic patients are associated to the epileptogenic focus localization].
Clinical and experimental data support the role of immune mechanisms in the pathogeny of epilepsy. The purpose of this work was to study the immunological aspects in 30 epileptic patients with complex partial crisis resistant to antiepileptic drugs. The patients were evaluated by EEG-Video and they were grouped attending to epileptogenic focus localization in: temporals (n = 16), lateralized (n = 6) and extratemporals (n = 4). We also studied a group with psychogenic epilepsy (n = 4), this group was diagnosed after EEG-video evaluation. The following immunological evaluations has been carried out: levels of serum immunoglobulins (IgG, IgM e IgA) by radial immunodiffusion test and lymphocytic subpopulations using immunocytochemical methods. We measured the percent of T and B lymphocytes (CD3 and CD20), helper/inductor lymphocyte T (CD4), suppressor/cytotoxic (CD8), interleukine-2 receptor (CD25) and human leukocyte antigen (HLA-DR). The results show a significant increase of CD8+ lymphocytes (p < 0.05) and in the activation markers (CD25+ and HLA-DR+ cells). The evaluation of immunological parameters applied to different group of epileptogenic focus localization shown that the increase of CD8+ lymphocytes is limited to temporal and lateralized patients (p < 0.01). The patients with extratemporal localization of focus and the psychogenic cases shown normal values for the evaluated immunological lymphocyte markers. We did not find a deficit in the humoral immunological aspects. Taking into account that patients diagnosed as psychogenic received an antiepileptic drug treatment identical to that of the other group, the observed immunological changes might be related with the patogeny of certain epilepsy variants associated with the focus localization and not with the medication.


Adaptive nanomechanical response of stratified polymer brush structures.
We have fabricated a stratified polymer surface film with tunable thickness (within 17-34 nm) through facile, room-temperature, UV-initiated polymerization with a temperature-sensitive pNIPAAM layer confined beneath a hydrophobic layer. AFM morphology and ellipsometric measurements were measured at each grafting step, along with XPS measurements of the overall layer to verify layer growth. The strong characteristic LCST behavior of pNIPAAM was observed in water, with a 100% change in thickness above and below this transition. The AFM nanomechanical results demonstrate vertical gradients of the elastic response tunable to a desired state by the external temperature. These temperature-sensitive, adaptive polymer structures with the pNIPAAM layer "hidden" beneath the rubbery, hydrophobic PBA topmost layer represent an interesting example of nanoengineering surfaces with properties such as adhesion, elastic modulus, and multi-level structural reorganization responsive to fluidic and temperature variations that can be important for biological purposes such as implant coatings, cell-surface mimicry, and drug delivery vehicles.


Functional role of the prokaryotic proline-tRNA synthetase insertion domain in amino acid editing.
Aminoacyl-tRNA synthetases catalyze the attachment of specific amino acids to cognate tRNAs in a two-step process that is critical for the faithful translation of genetic information. During the first chemical step of tRNA aminoacylation, noncognate amino acids that are smaller than or isosteric with the cognate substrate can be misactivated. Thus, to maintain high accuracy during protein translation, some synthetases have evolved an editing mechanism. Previously, we showed that class II Escherichia coli proline-tRNA synthetase (ProRS) is capable of (1) weakly misactivating Ala, (2) hydrolyzing the misactivated Ala-AMP in a reaction known as pretransfer editing, and (3) deacylating a mischarged Ala-tRNA(Pro) variant via a post-transfer editing pathway. In contrast to most systems where an editing function has been established, pretransfer editing by E. coli ProRS occurs in a tRNA-independent fashion. However, neither the pre- nor the post-transfer editing active site(s) has been identified. Sequence analyses revealed that most prokaryotic ProRSs possess a large insertion domain (INS) between class II conserved motifs 2 and 3. The function of the approximately 180-amino acid INS in E. coli ProRS is the subject of this investigation. Alignment-guided Ala scanning mutagenesis was carried out to test conserved amino acid residues present in the INS for their role in pre- and post-transfer editing. Our biochemical data and modeling studies suggest that the prokaryotic INS plays a critical role in editing and that this activity resides in a domain that is functionally and structurally distinct from the aminoacylation active site.


Analysis of eosinophil turnover in vivo reveals their active recruitment to and prolonged survival in the peritoneal cavity.
Eosinophils are potent effector cells associated with allergic inflammation and parasite infections. However, limited information exists about their turnover, migration, and survival in vivo. To address these important questions, we determined murine eosinophil turnover under steady state and inflammatory conditions by flow cytometric analysis of BrdU incorporation and analyzed their migration pattern and survival in different tissues after adoptive transfer into recipient mice. In naive mice approximately 50% of bone marrow eosinophils were labeled with BrdU during a 15-h pulse, whereas only 10% of splenic eosinophils were labeled within this time frame. Unexpectedly, the rate of eosinophil production did not change during acute infection with the helminth parasite Nippostrongylus brasiliensis despite massive eosinophilia in several tissues. Eosinophils present in lung and peritoneum remained largely BrdU negative, indicating that eosinophilia in end organs was mainly caused by increased survival of already existing eosinophils rather than increased production of new eosinophils in the bone marrow. Adoptive transfer experiments revealed that eosinophils preferentially migrated to the peritoneum in a macrophage-independent and pertussis toxin-sensitive manner, where they survived for several days. Peritoneal eosinophils expressed high levels of the inhibitory receptor Siglec-F, released less eosinophil peroxidase compared with eosinophils from the spleen, and could recirculate to other organs. These results demonstrate that the peritoneum serves as reservoir for eosinophils.


Studies on metacercariae from naiads in northeast Thailand.
One hundred and eleven naiads from six different dragonfly species were investigated for the presence of metacercariae. Sixty-nine animals (62.2%) were infected with intensities up to more than 150 cysts per animal. The metacercarial cysts were characterized by light and scanning electron microscopy. Two types of metacercariae could be differentiated by morphological features of cyst surface, cyst wall and size.


Skin heat dissipation: the influence of diabetes, skin thickness, and subcutaneous fat thickness.
It is well established that diabetes impairs vascular endothelial function. However, the impact of impaired endothelial function on thermal conductivity of the skin, especially in relation to a constant versus a sudden heat stress, has not been established. Further, there is some evidence that aging reduces skin dermal thickness and subcutaneous fat thickness. Since these are important determinates of heat dissipation by the skin, these parameters also need to be examined in people with diabetes. Ninety subjects (30 younger individuals, 30 patients with diabetes, and 30 patients age-matched to the diabetes subjects) participated in two series of experiments to determine (1) the thickness of the subcutaneous fat layer and skin thickness and the skin response to a sudden heat stress and (2) the response to a continuous heat stress on the lower back. Skin thickness and subcutaneous fat thickness were assessed by ultrasound, and skin blood flow was examined by infrared laser Doppler flow meter. People with diabetes had significantly less resting blood flow, blood flow in response to a single or continuous heat load, less subcutaneous fat, and thinner skin than either age-matched controls or younger people (P < 0.05). Subjects with diabetes also had the lowest concentration of red blood cells in their skin, implying a reduction in the number of capillaries in the skin. Thinning of the skin and probably a reduction in capillaries in the dermal layer contribute to a reduction in the blood flow response to heat. People with diabetes, in particular, have reduced skin heat dissipation because of less resting blood flow and thinner skin than that seen in age-matched controls.


CD8+ T Cells Effect Glomerular Injury in Experimental Anti-Myeloperoxidase GN.
Observations in patients with ANCA-associated vasculitis suggest that CD8+ T cells participate in disease, but there is no experimental functional evidence of pathologic involvement for these cells. Myeloperoxidase (MPO) is a well defined autoantigen in ANCA-associated vasculitis. Studies in experimental models of anti-MPO GN suggest that, after ANCA-induced neutrophil localization, deposited MPO within glomeruli is recognized by autoreactive T cells that contribute to injury. We tested the hypothesis that CD8+ T cells mediate disease in experimental ANCA-associated vasculitis. CD8+ T cell depletion in the effector phase of disease attenuated injury in murine anti-MPO GN. This protection associated with decreased levels of intrarenal IFN-γ, TNF, and inflammatory chemokines and fewer glomerular macrophages. Moreover, we identified a pathogenic CD8+ T cell MPO epitope (MPO431-439) and found that cotransfer of MPO431-439-specific CD8+ T cell clones exacerbated disease mediated by MPO-specific CD4+ cells in Rag1-/- mice. Transfer of MPO431-439-specific CD8+ cells without CD4+ cells mediated glomerular injury when MPO was planted in glomeruli. These results show a pathogenic role for MPO-specific CD8+ T cells, provide evidence that CD8+ cells are a therapeutic target in ANCA-associated vasculitis, and suggest that a molecular hotspot within the MPO molecule contains important CD8+, CD4+, and B cell epitopes.


Reducing Dental Plaque and Gingivitis With 0.6% Cortex Ilicis Rotundae Toothpaste: A Randomized, Double-Masked Clinical Trial.
Cortex Ilicis Rotundae has antioxidant and anti-inflammatory properties. Few studies have evaluated the effects of toothpastes containing Cortex Ilicis Rotundae. This study evaluates the antiplaque and antigingivitis effects of a test toothpaste containing 0.6% Cortex Ilicis Rotundae extract in a calcium carbonate base compared with a control toothpaste without any active ingredient. One hundred adults with a mean plaque index (PI) ≥ 1.5 and a mean gingival index (GI) ≥ 1.0 were enrolled in this randomized, double-masked, placebo-controlled clinical trial. They were assigned randomly to use a test toothpaste or a control toothpaste. At baseline, 6 weeks, and 12 weeks, they received examinations of oral hard and soft tissues, using Löe-Silness GI for gingivitis and the Turesky modification of the Quigley-Hein PI for PI. Adverse events were monitored. When the study was completed, the test group reported lower mean GI than the control group (1.13 ± 0.22 versus 1.30 ± 0.23; P = 0.001) and lower mean PI than the control group (2.53 ± 0.5 versus 2.93 ± 0.44; P < 0.001). Compared to the baseline, the test group had reductions in GI and PI of 14.39% and 17.86%, respectively (both P < 0.001); the control group had reductions in GI and PI of 3.7% and 3.93%, respectively (both P < 0.001). No adverse events were reported during the course of the study. The toothpaste containing 0.6% Cortex Ilicis Rotundae was effective in reducing dental plaque and gingivitis after 12 weeks of use compared with a negative control toothpaste.


Physical activity and fetal growth during pregnancy.
To assess the separate and combined relationships of aerobic physical activity during pregnancy, maternal weight gain during pregnancy, and height to the fetal growth ratio. The aerobic physical activity of 51 healthy, nonsmoking pregnant women was assessed for 48 hours at both 20 and 32 weeks of pregnancy by accelerometry, heart rate monitoring, and physical activity recall. We analyzed the relationship between maternal physical activity and the fetal growth ratio. All women included in the analysis completed healthy, uncomplicated pregnancies and delivered infants with a weight range of 2,743-4,943 g. Aerobic physical activity assessed by accelerometry was strongly and inversely associated with fetal growth ratio (r=-0.42; P<.002). Infants born to women in the highest quartile of physical activity weighed 608 g less than infants born to women in the lowest quartile. The inverse relationship between physical activity and fetal growth ratio was moderated by maternal height; virtually all the effect was seen in mothers taller than the sample median (1.65 m). Similar relationships were found across methods of physical activity measurement. Aerobic physical activity in pregnancy may be an important determinant of birth weight within the normal range, especially in taller mothers. II.


[Aplasia cutis congenita is a rare and possibly overlooked congenital anomaly].
Aplasia cutis congenita (ACC) is a rare congenital defect of the skin. In this study we present the diagnosis and management of the condition. In 1997-2009 a total of 65 ACC cases were registered in the Danish National Patient Registry (1:13.000 births). The mortality among these cases was 1.6% (one case) though the death was not attributable to ACC, which is far lower than described in international studies.


Practical use of airway pressure release ventilation for severe ARDS--a preliminary report in comparison with a conventional ventilatory support.
Airway pressure release ventilation (APRV) is a ventilatory mode that allows unsupported spontaneous breathing at any phase of the ventilatory cycle with high mean airway pressures. We hypothesized that use of APRV might produce potential beneficial effects on oxygenation, reducing mortality in patients with severe acute respiratory distress syndrome (ARDS) in comparison with synchronized intermittent mandatory ventilation (SIMV) as a conventional mode of ventilation. We retrospectively reviewed data of 58 patients with severe ARDS (the ratios of partial arterial oxygen tension to fraction of inspired oxygen, PaO2/F(I)O2 ratio <150). The patients' data were divided into two groups: SIMV-group and APRV-group. Patients' backgrounds, oxygenation on day 0, 1, 3, 5 and 7 following initiation of each mode, vasopressor dependence, duration of ventilation, duration of ICU stay, and mortality in ICU were analyzed. PaO2/F(I)O2 ratios were statistically higher in the APRV-group (APRV vs. SIMV on day 1, 3, 5, 7: 201.6 +/- 76 vs.150 +/- 59.1, 256.7 +/- 71.5 vs.182.1 +/- 65.4, 268.8 +/- 73.3 vs. 204.6 +/- 72.8, and 263 +/- 74.5 vs. 204.1 +/- 67.1, respectively, p<0.05). Vasopressors were less used (p=0.018), and mortality in ICU tended to be lower in the APRV group (31%) than in the SIMV group (59%) (p=0.050). Use of APRV in patients with severe ARDS appears to be associated with improvements in oxygenation, and a trend toward lower mortality in ICU. No significant adverse effects were observed. Prospective controlled studies are required to confirm the benefits of this ventilatory mode in comparison with conventional methods for severe ARDS.


Umbilical cord-derived mesenchymal stem cell transplantation in vaginal replacement in vitro and in a rat model.
Cell transplantation strategies represent a potential therapeutic approach towards repair of congenital vaginal agenesis. In this study, the efficacy and mechanisms of action of treatment with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on vaginal regeneration was explored. UC-MSC transplantation alone, small intestinal submucosal (SIS) grafting alone, and a combination of UC-MSC transplantation/SIS grafting were performed with a vaginal defect rat model. Histological analyses of tissue sections were subsequently performed. UC-MSCs promoted the recovery of keratinizing squamous epithelium and papillae to nearly the same levels as in normal tissue. Of the treatments tested, UC-MSC transplantation showed optimal performance in inhibiting collagen deposition and accelerating the synthesis of elastin to maintain tissue elasticity. UC-MSC treatment also increased Cyclin D1, Ki67, and CD31 expression as assessed by immunohistochemistry. We also investigated the effects of UC-MSC secretions on keratinocytes in a co-culture model. UC-MSCs significantly stimulated vaginal tissue repair by promoting vaginal epithelium regeneration via paracrine factors but not by exploiting their keratinocyte differentiation potential. Further, UC-MSCs facilitated epithelial cell viability and promoted cell cycle progression via the AKT/GSK3β/Cyclin D1 pathway. These results indicate that UC-MSC transplantation is a feasible approach for vaginal tissue regeneration.


Maternal diet quality and nutrient intakes across preconception and pregnancy are not consistent with Australian guidelines: Results from the pilot BABY1000 study.
Maternal nutrition has profound and lasting effects on growth and health from infancy into adulthood. The aim of this manuscript was to assess diet quality and nutrient adequacy in preconception and pregnancy in BABY1000 pilot study participants (n = 171). The Australian Eating Survey (AES) Food Frequency Questionnaire was administered to women based in Sydney, Australia, at preconception or 12 weeks' gestation (n = 158), and again at 36 weeks' gestation (n = 99). Primary outcomes were diet quality and nutrient intake. Diet quality was evaluated using the AES diet quality subscale, the Australian Recommended Food Score (ARFS). Nutrient intakes were compared to Australian Nutrient Reference Values. Diet quality and nutrient intakes were not consistent with Australian recommendations. Over 83% of women exceeded the suggested target limits for percentage energy from saturated fat. Median ARFS was 37 at baseline, and 38 in late pregnancy (maximum score 73). Inadequate micronutrient intakes from food were common; no participants met the Estimated Average Requirement for iron, 76%-84% for iodine, 70%-78% for calcium and 44%-50% for folate. Maternal diet quality and nutrient intakes in the current sample are inconsistent with pregnancy recommendations and therefore may not be supporting optimal perinatal or long-term offspring health. Stronger messaging around the importance of prenatal nutrition, prevalence of dietary inadequacy, and availability of reliable support and information specific to nutrition in pregnancy is crucial in supporting women to improve their nutrition both before and during pregnancy.


Real-time digital angiocardiography using a temporal high-pass filter.
A temporal high-pass filtration technique for digital subtraction angiocardiography was studied, using real-time digital studies performed simultaneously with routine cineangiocardiography (cine) for qualitative image comparison. The digital studies showed increased contrast and suppression of background anatomy and also enhanced detection of wall motion abnormalities when compared with cine. This digital technique is compatible with panning the image intensifier during an injection. The digital images are comparable with, and in some cases better than, cine images. Clinical efficacy of this digital technique is currently being evaluated. Real-time display, as well as potential reductions in radiation and contrast material doses, may make digital angiocardiography an attractive technique.


Evaluating Weight Status and Sex as Moderators of the Association of Serum Leptin with Bone Mineral Density in Children and Adolescents .
Animal studies suggest that leptin may adversely affect bone mineral density (BMD). Clinical studies have yielded conflicting results. We therefore investigated associations between leptin and bone parameters in children. 830 healthy children (age = 11.4 ± 3.1 years; 75% female; BMI standard deviation score [BMIz] = 1.5 ± 1.1) had fasting serum leptin measured with ELISA and body composition by dual-energy X-ray absorptiometry. The main effects for leptin and BMIz plus leptin's interactions with sex and BMIz were examined using hierarchical linear regressions for appendicular, pelvis, and lumbar spine BMD as well as bone mineral content (BMC), and bone area (BA). Accounting for demographic, pubertal development, and anthropometric variables, leptin was negatively and independently associated with lumbar spine BMC and BA, pelvis BA, and leg BA (p < 0.05 for all). Sex, but not BMIz, moderated the associations of leptin with bone parameters. In boys, leptin was negatively correlated with leg and arm BMD, BMC at all bone sites, and BA at the subtotal and lumbar spine (p < 0.01 for all). In girls, leptin was positively correlated with leg and arm BMD (p < 0.05 for both). Independent of body size, leptin is negatively associated with bone measures; however, these associations are moderated by sex: boys, but not girls, have a negative independent association between leptin and BMD. .


Classically conditioned changes of blood glucose level.
This paper reviews the literature dealing with classically conditioned changes of blood glucose level. When conditioning procedures are employed, the repeated administration of large amounts of insulin, or of glucose, leads to a conditioned decrease of blood glucose whereas the repeated administration of smaller amounts of insulin leads to a conditioned increase of glucose. These responses are interpreted as instances of reflex compensation by the central nervous system for rapid alterations of glucose availability. Instances of more naturally occurring changes of glucose levels, which appear to be under the control of the nervous system and to be conditionable, are also discussed. A model that accounts for the observed responses has been formulated and is presented.


Flavonoids and Melanins: a common strategy across two kingdoms.
Ultraviolet (UV) radiations alter a number of metabolic functions in vivant. They produce damages to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O2), hydroxyl radical (HO) and superoxide anion (O2 (-)). Plants and animals, after their water emersion, have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments acting as free radical scavenging mechanisms. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation. Noteworthy, beside anti-oxidant scavenging activity, melanins and flavonoids have acquired secondary functions that, both in plants and animals, concern reproductions and fitness. Plants highly pigmented are more resistant to biotic and abiotic stresses. Darker wild vertebrates are generally more aggressive, sexually active and resistant to stress than lighter individuals. Flavonoids have been associated with signal attraction between flowers and insects and with plant-plant interaction. Melanin pigmentation has been proposed as trait in bird communication, acting as honest signals of quality. This review shows how the molecular mechanisms leading to tissue pigmentation have many functional analogies between plants and animals and how their origin lies in simpler organisms such as Cyanobacteria. Comparative studies between plant and animal kingdoms can reveal new insight of the antioxidant strategies in vivant.


Inhibitory effect of brazilin on osteoclast differentiation and its mechanism of action.
Brazilin isolated from Caesalpinia sappan has long been known as a natural red pigment. Our study evaluated the inhibitory effect of brazilin on osteoclast differentiation and investigated its mechanism of action. Our results demonstrated that brazilin inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation in RAW264.7 cells in a dose-dependent manner, without any evidence of cytotoxicity. The mRNA expression of tartrate-resistant acid phosphatase (TRAP), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), matrix metalloproteinase 9 (MMP-9), and cathepsin K in RANKL-treated RAW264.7 cells was inhibited by brazilin treatment. Brazilin also decreased RANKL-induced expression of inflammatory mediator genes such as inducible nitric oxide synthase, iNOS; cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 and inhibited extracellular signal-regulated kinases (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) p65 phosphorylation in RANKL-stimulated RAW264.7 cells. A lipopolysaccharide (LPS)-induced osteoporosis study was also performed to assess the effects of brazilin in vivo. Micro-computed tomography (CT) analysis of the femurs showed that LPS treatment causes bone loss in mice, but it was significantly attenuated after co-treatment with brazilin (100mg/kg). Therefore, brazilin may have therapeutic potential in preventing bone loss.


3D micropattern force triggers YAP nuclear entry by transport across nuclear pores and modulates stem cells paracrine.
Biophysical cues of the cellular microenvironment tremendously influence cell behavior by mechanotransduction. However, it is still unclear how cells sense and transduce the mechanical signals from 3D geometry to regulate cell function. Here, the mechanotransduction of human mesenchymal stem cells (MSCs) triggered by 3D micropatterns and its effect on the paracrine of MSCs are systematically investigated. Our findings show that 3D micropattern force could influence the spatial reorganization of the cytoskeleton, leading to different local forces which mediate nucleus alteration such as orientation, morphology, expression of Lamin A/C and chromatin condensation. Specifically, in the triangular prism and cuboid micropatterns, the ordered F-actin fibers are distributed over and fully transmit compressive forces to the nucleus, which results in nuclear flattening and stretching of nuclear pores, thus enhancing the nuclear import of YES-associated protein (YAP). Furthermore, the activation of YAP significantly enhances the paracrine of MSCs and upregulates the secretion of angiogenic growth factors. In contrast, the fewer compressive forces on the nucleus in cylinder and cube micropatterns cause less YAP entering the nucleus. The skin repair experiment provides the first in vivo evidence that enhanced MSCs paracrine by 3D geometry significantly promotes tissue regeneration. The current study contributes to understanding the in-depth mechanisms of mechanical signals affecting cell function and provides inspiration for innovative design of biomaterials.


Clinical characteristics of people presenting with first episode psychosis pre- and during the COVID-19 pandemic in KwaZulu-Natal Province, South Africa.
The COVID-19 pandemic and the lockdown experience may have not only precipitated or exacerbated mental illness but also influenced access to care and the nature and content of the psychotic symptomatology of people with psychosis. This study aimed to evaluate the association of the COVID-19 pandemic and lockdown experience on clinical presentation and quality of life of people (QOL) with first episode psychosis (FEP). Two first episode psychosis cohorts from the same epidemiological area collected prior to, and during the COVID-19 pandemic and lockdown were compared in terms of clinical symptomatology, substance use and QOL. All adult in- and outpatients with FEP at five clinical units in KwaZulu-Natal, South Africa, aged between 18 and 45 years, were assessed with the MINI interview for psychosis, Positive and Negative Symptoms Scale, WHO Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the WHO QOL scales. Eighty-eight FEP participants were recruited between 2019 and 2020 (cohort 1) before the pandemic. Study recruitment was suspended in March 2020 due to the pandemic. On study resumption from November 2020 to November 2022, 95 new participants (cohort 2) were recruited. There were no sociodemographic differences between the two cohorts, except unemployment status (57% vs. 65%) and household income. The cohort presenting post-COVID-19 pandemic onset had significantly more positive psychotic symptoms (21.9 vs. 23.7), lower PANSS domain depressive score, more lifetime use of tobacco, cannabis and alcohol. However, they reported improved QOL (196 vs. 239). Following the pandemic and lockdown experience participants presented with more severe psychotic symptoms and concomitant substance use but improved perceived QOL. This suggests the need to explore individual and social factors that may influence the clinical presentation.


The relationship of MMPI and Sensation Seeking Scales to adolescent drug use.
This study examined the relationship of Minnesota Multiphasic Personality Inventory (MMPI) measures, including the MacAndrew alcoholism (MAC) scale, and the Sensation Seeking Scales (SSS) to adolescents' drug use across nine drug categories. Subjects were 51 male and 72 female high school students between the ages of 14 and 18 (mean age = 16 years, 5 months). The drug use/abuse measure consisted of adolescents' self-reports on the Segal (1973) Alcohol-Drug Use Research Survey. Drug categories included for investigation were alcohol, amphetamines, barbiturates, caffeine, cocaine, hallucinogens, marijuana, narcotics, and tobacco. Scores from standard MMPI scales, the MAC scale, and the SSS were examined in relation to individual drug use outcomes, and multivariate procedures were used to predict polydrug versus single drug use patterns. Results demonstrated significant and meaningful relationships between personality measures and drug use among adolescents, with consistently strong findings for the SSS.


Are Treatment Outcomes Determined by Type of Gambling? A UK Study.
One of the main difficulties faced in treating gambling disorder is compliance with psychological treatment. Gambling takes many forms and can differ greatly in its features such as speed of play and skill requirements. The type of gambling a pathological gambler opts for may play a key role in treatment compliance. The aim of the present study was to determine whether within treatment seeking sample of gambling disorder clients, gambling activity has any correlation with their resultant treatment outcomes. The study incorporated 524 treatment-seeking individuals who are clients of the National Problem Gambling Clinic in London. All of the clients were assessed prior to treatment and fulfilled the Problem Gambling Severity Index criteria for problem gambling. Data concerning clients' gambling behavior over the previous year was gathered using self-reports. Subsequently, the data was fitted to a multinomial logistic regression model, with the treatment outcome (i.e. pre-treatment dropouts, during treatment dropouts, and completed treatment) as the dependent variable and gambling behavior as the independent variable, whilst controlling for socio-demographic factors. The use of gaming machines was a significant predictor of dropping out pre-treatment (p < 0.05, RRR 1.616), whilst betting on sports events was a significant predictor of dropping out during treatment (p < 0.01, RRR 2.435). Treatment outcomes have been found to significantly differ based on participation in certain gambling activities. Further research into the salient features of these gambling activities may help to further explain pre-treatment and during treatment dropouts within this population.


Strong as a Hippo's Heart: Biomechanical Hippo Signaling During Zebrafish Cardiac Development.
The heart is comprised of multiple tissues that contribute to its physiological functions. During development, the growth of myocardium and endocardium is coupled and morphogenetic processes within these separate tissue layers are integrated. Here, we discuss the roles of mechanosensitive Hippo signaling in growth and morphogenesis of the zebrafish heart. Hippo signaling is involved in defining numbers of cardiac progenitor cells derived from the secondary heart field, in restricting the growth of the epicardium, and in guiding trabeculation and outflow tract formation. Recent work also shows that myocardial chamber dimensions serve as a blueprint for Hippo signaling-dependent growth of the endocardium. Evidently, Hippo pathway components act at the crossroads of various signaling pathways involved in embryonic zebrafish heart development. Elucidating how biomechanical Hippo signaling guides heart morphogenesis has direct implications for our understanding of cardiac physiology and pathophysiology.


Angiogenic activity as a marker of neoplastic and preneoplastic lesions of the human bladder.
Angiogenic activity has been assessed in biopsy specimens from 49 patients with transitional cell carcinoma, benign prostatic hypertrophy and vesicoureteral reflux. Over 95% of the specimens containing malignant and premalignant transitional epithelium stimulated capillary proliferation on rabbit iris. In contrast, less than 10% of normal tissues had this effect. Sixty-one per cent of specimens with inflammatory round cells were angiogenic but this was reduced to 10% by preincubation with rabbit antihuman lymphocyte serum. Cystitis cystica also induced capillary proliferation even if incubated with the antilymphocyte serum. Angiogenic capacity may be an early marker of preneoplastic and neoplastic lesions of the human bladder.


[The psychiatric forms of Creutzfeldt-Jakob disease].
Frequent in the new variant of Creutzfeldt-Jakob disease, psychiatric disorders are less common in the sporadic form. The disorders are non-specific: mood disorders, personality changes and psychotic symptoms. The diagnosis of Creutzfeldt-Jakob disease is evoked on the emergence of the first neurological signs, notably ataxia and myoclonia. The diagnosis is supported by the search for P 14-3-3, EEG in the cerebrospinal liquid as well as electroencephalogram and magnetic imaging that permit distinction between the sporadic and the new variant forms.


Lack of evidence for association of high altitude pulmonary edema and polymorphisms of the NO pathway.
One essential factor in the development of high altitude pulmonary edema (HAPE) is elevated pulmonary artery pressure, possibly due to a lack of nitric oxide (NO) in pulmonary vessels. NOS3 gene polymorphisms (G894T, T-786C, and CA-repeats > or =38) might be linked to decreased NO synthesis and increased susceptibility to HAPE, while the C242T polymorphism of the CYBA gene [encoding for the NAD(P)H oxidase subunit p22phox] may increase NO availability and thus convey resistance to HAPE. To test this hypothesis, we genotyped 51 mountaineers susceptible and 52 mountaineers not susceptible to HAPE. Genotyping revealed similar genotype frequencies of the G894T and the T-786C NOS3 polymorphism in both groups (G894T: susceptibles, 39.2% GG, 47.1% GT, 13.7% TT; nonsusceptibles, 48.0% GG, 44.0% GT, 8.0% TT; p = 0.54. T-786C: susceptibles, 45.1% TT, 39.2% TC, 15.7% CC; nonsusceptibles, 53.8% TT, 40.4% TC, 5.8% CC; p = 0.28). Genotype frequencies of the C242T CYBA polymorphism were 43.1% CC, 47.1 % CT, and 9.8% TT in HAPE susceptibles and 38.0% CC, 52.0 % CT, and 10.0% TT (p = 0.92) in nonsusceptibles. There was also no difference between the two groups in the number of CA repeats (p = 0.57), and individuals with > or =38 CA repeats were not more likely to develop HAPE (p = 1.0). Haplotype analysis for the NOS3 polymorphisms also revealed no association with HAPE. The results of this study suggest that none of these genetic variants plays a substantial role in the pathogenesis of HAPE in Caucasians, but does not exclude epistatic effects that might still involve the genetic systems studied here.


Polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) in Italian food: Occurrence and dietary exposure.
Human exposure to polychlorinated dioxins and furans (PCDD/Fs) through the dietary pathway is widely recognised and regulations in some regions of the world help to limit food contamination. Similar information on the analogous polybrominated dioxins and furans (PBDD/Fs) is scarce, partly due to the higher threshold to analytical access and unavailability of some standard materials. The analytical methodology developed here determined twelve planar PBDD/F congeners using 13Carbon labelled PBDD/F surrogates and high resolution mass spectrometric detection, and was extensively validated prior to the analysis of a range of commonly consumed Italian foods. The methodology also allowed simultaneous determination of PCDD/Fs and polychlorinated biphenyls (PCBs). The results show that PBDD/Fs occurred in different foods over a range of concentrations from <0.001 pg/g to 4.58 pg/g in fish. The dietary exposure (upper bound) of different Italian population groups, resulting from these occurrence levels was estimated using the toxic equivalency (TEQ) approach that is commonly used for dioxin-like contaminants and ranged from 0.17 to 0.42 pg TEQ/kg bodyweight/day (lower bound - 0.01 pg TEQ/kg bodyweight/day) depending on the population subgroup. Although precautionary, upper bound values may provide a more realistic estimate of toxicity as not all congeners and foods were measured. As expected, children were more highly exposed than adults due to lower body weight. These exposure levels were between a quarter and a third of that arising from the sum of PCDD/Fs and PCBs (0.61 to 1.38 pg WHO-TEQ/kg bodyweight/day), but they contribute to dioxin-like toxicity. If this data is considered in view of the revised tolerable dioxin-like dietary intake published by EFSA in 2018, it is evident that the tolerable weekly intake of 2 pg/kg bodyweight/week would be exceeded by some of the assessed population sub-groups, or all sub-groups if the cumulative intake is considered.


Vietnamese version of the coronary artery disease education questionnaire-Short version: Translation, adaptation and validation.
Coronary artery disease (CAD) is the leading cause of mortality worldwide. Patient education is an essential part of cardiac patients' care targeting self-management behaviour to reduce risk factors and subsequent events. There has been no Vietnamese questionnaire to assess patient's knowledge about CAD; therefore, the purpose of this study was to translate, cross-culturally adapt and validate the Coronary Artery Disease Education Questionnaire-Short Version (CADE-Q SV) for use in Vietnam. Translation and cross-cultural adaption of the tool were carried out in five stages: (a) two independent translations from English into Vietnamese were produced; (b) these two translations were then synthesized; (c) two translators blinded to the outcome measurements independently created separate back translations into English; (d) nine experts reached consensus on all items of the Vietnamese version of the CADE-Q SV; and (e) a pilot study was conducted on 35 patients with acute coronary syndrome (ACS). The validity and reliability of the questionnaires were then evaluated in 117 Vietnamese patients with ACS. The internal consistency and test-retest reliability were assessed by Cronbach's alpha and Cohen's kappa coefficient, respectively. Construct validity was determined by examining the relationship between knowledge scores and patient characteristics. The Vietnamese version of CADE-Q SV was created, including 20 items divided into two domains: medical and psychological condition, and nutrition and exercise. There was good equivalence between the original and the Vietnamese versions in all four areas: semantic, idiomatic, experiential and conceptual equivalence. Cronbach's alpha coefficients were acceptable for the questionnaire as a whole (0.78) and for the two domains: medical and psychological condition (0.71) and nutrition and exercise (0.52). All Cohen's kappa coefficients confirmed test-retest reliability (Kappa > 0.600; P < .001). Construct validity was confirmed by a significant correlation of knowledge scores with education level (P = .004). The Vietnamese version of CADE-Q SV can be considered a valid and reliable questionnaire to evaluate patient's knowledge of CAD. Further studies could investigate the influence of knowledge scores on adherence to medications and clinical outcomes of patients with CAD.


[Incorporation of [2-14C orotic] acid into chromatin RNA of tissues of animals of various ages].
The structure and biological activity (the level of the labelled precursor incorporation into RNA) of active and repressed chromatin of the liver and small intestine mucosa were studied in adult (6-8 months) and old (24-26 months) rats. The content of repressed chromatin fraction in both tissues is found to increase with age. In the liver of old rats the level of [14C[ orotic acid incorporation into RNA of chromatin fractions decreases, radioactivity of the acid-soluble fraction being unchanged. In the small intestine mucosa a high leve of [14C] orotic acid incorporation into chromatin RNA with ageing is due to an increase in permeability of the mucosa cells.


A descriptive study of self-medication practices among Sri Lankan national level athletes.
Intake of medicines and supplements is widespread among the professional athletes in developed countries and there are reports to suggest inappropriate self-administration of medicine. Data from South Asia on this area is lacking. This study examined self-medication practices with regard to use of allopathic and herbal/traditional medicines among national -level Sri Lankan athletes. 209 athletes from 15 national sport teams were assessed using an anonymous, interviewer administered questionnaire. Self-medication practices during the 3 months before data collection were evaluated. 60.8% athletes practiced self-medication. 58.3 and 9.4% consumed western and herbal/traditional medicines respectively, while a third used both. The most common symptom for which self-medication was practiced was musculoskeletal pain (73.2%). Oral non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics were used by 15.7 and 7.1% respectively. Musculoskeletal pain was the predominant symptom that prompted the use of allopathic medicines, while the majority of athletes with upper respiratory tract symptoms being the predominant symptoms, consumed herbal/traditional medicines. Two different commercially available preparations of herbal mixtures were consumed by 15.7 and 15%. Pain prophylaxis during or prior to a sport event was reported by 20.1%, mainly with topical medicines. Medicines were obtained by direct request from a pharmacy without an authorized prescription by a majority (77.2%), followed by using an old prescription in 12.6%. This study finds that self-medication with both allopathic and herbal/traditional preparations among athletes in a Sri Lanka is high. The use of oral NSAIDs without an authorized prescription in a significant number of athletes is a potential health risk. Frequency of oral NSAID use is lower than that is reported in non-Asian studies from developed countries. The use of herbal/traditional medications increases the likelihood of inadvertent doping. Enhancing awareness regarding risk of such practices among athletes, trainers, pharmacists and prescribers is essential.


Influence of felbamate on the antinociceptive action of morphine, metamizol and indomethacin in mice.
The influence of felbamate (200 mg/kg or 50 mg/kg) on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg or 1.4 mg/kg) was investigated in a mouse model using the hot-plate test. All drugs were injected intraperitoneally. Felbamate was administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after felbamate administration. The research studies were further conducted with a multiple (10 days) drug dosage. Felbamate in the dose of 200 mg/kg significantly increases the analgesic effect of morphine and weakens the effect of metamizol and indomethacin. Multiple administration of felbamate does not affect the activity of morphine and metamizol, but decreases analgesic effect of indomethacin.


Refugee Mental Health, Global Health Policy, and the Syrian Crisis.
The most recent global refugee figures are staggering, with over 82.4 million people forcibly displaced and 26.4 million registered refugees. The ongoing conflict in Syria is a major contributor. After a decade of violence and destabilization, over 13.4 million Syrians have been displaced, including 6.7 million internally displaced persons and 6.7 million refugees registered in other countries. Beyond the immediate political and economic challenges, an essential component of any response to this humanitarian crisis must be health-related, including policies and interventions specific to mental health. This policy and practice review addresses refugee mental health in the context of the Syrian crisis, providing an update and overview of the current situation while exploring new initiatives in mental health research and global health policy that can help strengthen and expand services. Relevant global health policy frameworks are first briefly introduced, followed by a short summary of recent research on refugee mental health. We then provide an update on the current status of research, service provision, and health policy in the leading destinations for Syrians who have been forcibly displaced. This starts within Syria and then turns to Turkey, Lebanon, Jordan, and Germany. Finally, several general recommendations are discussed, including the pressing need for more data at each phase of migration, the expansion of integrated mental health services, and the explicit inclusion and prioritization of refugee mental health in national and global health policy.


Barriers and opportunities to increase PD incidence and prevalence: Lessons from a European Survey.
Peritoneal dialysis (PD) remains underutilised and unplanned start of dialysis further diminishes the likelihood of patients starting on PD, although outcomes are equal to haemodialysis (HD). A survey was sent to members of EuroPD and regional societies presenting a case vignette of a 48-year-old woman not previously known to the nephrology department and who arrives at the emergency department with established end-stage kidney disease (unplanned start), asking which dialysis modality would most likely be chosen at their respective centre. We assessed associations between the modality choices for this case vignette and centre characteristics and PD-related practices. Of 575 respondents, 32.8%, 32.2% and 35.0% indicated they would start unplanned PD, unplanned HD or unplanned HD with intention to educate patient on PD later, respectively. Likelihood for unplanned start of PD was only associated with quality of structure of the pre-dialysis program. Structure of pre-dialysis education program, PD program in general, likelihood to provide education on PD to unplanned starters, good collaboration with the PD access team and taking initiatives to enhance home-based therapies increased the likelihood unplanned patients would end up on PD. Well-structured pre-dialysis education on PD as a modality, good connections to dedicated PD catheter placement teams and additional initiatives to enhance home-based therapies are key to grow PD programs. Centres motivated to grow their PD programs seem to find solutions to do so.


A Comparison of Endoscopic Reduction for Medial Blowout Fractures Using a Bioresorbable Panel and Silastic Sheet.
The aim of the study was to compare the effectiveness of endoscopic endonasal reduction using a bioresorbable panel and silastic sheet packed with Merocel for blowout fractures of the medial orbital wall. Retrospective study. The study group consisted of 147 patients who underwent endoscopic endonasal reduction of a blowout fracture of the medial orbital wall between January 2005 and December 2016. Fifty-seven fractures were repaired using a splint formed by a silastic sheet and Merocel (splint group), whereas 90 fractures were repaired using a bioresorbable panel for interposition (interposition group). Postoperative complications and surgical outcomes of the 2 groups were compared. Preoperative diplopia in both groups (n = 30) was resolved except 1 in interposition group after the reduction. Enophthalmos was resolved in 10 cases in the splint group and in 6 cases in the interposition group. In postoperative CT scans, 20 of the 57 cases in the splint group exhibited under- or overcorrection, compared with 9 of the 90 cases in the interposition group (P < 0.05). There were no sinus infections or implant-related side effects in the interposition group except for implant extrusion in 4 cases, whereas 7 cases developed sinusitis in the splint group (P < 0.05). Endonasal endoscopic reduction using a bioresorbable panel may be considered as a surgical alternative for the treatment of medial orbital blowout fractures.