The treatment of low retrosternal tracheal stenosis in the neonate and small children.
In the years 1979 to 1983, 8 infants or small children under 2 years of age were treated for severe low retrosternal (carinal) tracheal stenosis. The etiology was iatrogenic (postintubation) in 7 cases and congenital in one. Low tracheal stenosis was seen in 0.4% of all intubated (1607 patients) neonates during the same time period. In 6 cases of acute obstruction, diagnostic bronchoscopy was used to relieve the stenosis by forcefully dilating the trachea. One patient died and all had severe complications, but 3 children are living and doing well without further treatment. Only short granular retrosternal stenoses appeared to be suitable for violent dilatation, which is indicated if the patient is otherwise facing death due to suffocation. All other operative facilities must be at hand. Resection of low retrosternal trachea under cardiopulmonary bypass was performed in 4 patients - 2 of them had had earlier unsuccessful dilatations. One patient, aged 1.5 months, died. In this case the obstruction extended into both bronchi. Another patient was re-resected with success. The follow-up time of the 3 living patients with resection is already 2.4, 4.5 and 4.7 years respectively. The patients are living a normal life and the anastomoses are growing normally.


Drought stress, growth and nonstructural carbohydrate dynamics of pine trees in a semi-arid forest.
In trees exposed to prolonged drought, both carbon uptake (C source) and growth (C sink) typically decrease. This correlation raises two important questions: (i) to what degree is tree growth limited by C availability; and (ii) is growth limited by concurrent C storage (e.g., as nonstructural carbohydrates, NSC)? To test the relationships between drought, growth and C reserves, we monitored the changes in NSC levels and constructed stem growth chronologies of mature Pinus halepensis Miller trees of three drought stress levels growing in Yatir forest, Israel, at the dry distribution limit of forests. Moderately stressed and stressed trees showed 34 and 14% of the stem growth, 71 and 31% of the sap flux density, and 79 and 66% of the final needle length of healthy trees in 2012. In spite of these large reductions in growth and sap flow, both starch and soluble sugar concentrations in the branches of these trees were similar in all trees throughout the dry season (2-4% dry mass). At the same time, the root starch concentrations of moderately stressed and stressed trees were 47 and 58% of those of healthy trees, but never <2% dry mass. Our results show that all the studied trees maintain a fairly good coordination between C supply and demand, and even during prolonged drought there is more than one way for a tree to maintain a positive C balance.


'I can hardly breathe': Exploring the parental experience of having a child with a functional disorder.
Functional disorders in children and adolescents are common. Still, little is known about parents' experience of having a child with a functional disorder. The aim of this qualitative interview study was to explore challenges encountered by parents caring for a child undergoing treatment for functional disorder. Sixteen parents to children with functional disorders were interviewed when their child was referred from a paediatric department for further specialized treatment with family therapy in child and adolescent mental health services. Analysis identified three themes, reflecting the parental experiences: parents in limbo, which described how limited knowledge about functional disorders among professionals in non-specialized settings influenced parental roles; a counterintuitive kind of caring, describing parental struggles with adhering to treatment recommendations for functional disorders; and challenges to parental identity, describing parental emotional challenges. These challenges may bar the acceptance of psychological treatment approaches in families with a child with functional disorders.


Skin cancer preventive behaviors among rural farmers: An intervention based on protection motivation theory.
Background: Skin cancer is a serious public health problem in the world. Its prevalence in many countries has been increased in recent years. This study aimed to assess the effects of a theory-based educational intervention to promote skin cancer preventive behaviors (SCPBs) among rural farmers in Chalderan County, Iran. Methods: This was a quasi-randomized controlled field trial study conducted on 238 rural farmers. The data were collected by a questionnaire containing the constructs of the Protection Motivation Theory (PMT) as well as the items of SCPBs. The differences between the groups before and 3 months after the intervention were determined by independent t-test, paired t-test, and chi-square applying SPSS software. Results: Before the intervention, no significant difference was found in the scores of the PMT constructs between the two groups (p>0.05). However, significant differences were found between the scores of all the variables, as well as SCPBs, in the two groups after the intervention (p<0.05). Conclusion: The PMT was found to be an appropriate framework for designing educational interventions aiming at promoting SCPBs among rural farmers. It was concluded that designing an educational program with a focus on promoting perceived susceptibility increased the level of performing SCPBs among the rural farmers.


FTI-277 and GGTI-289 induce apoptosis via inhibition of the Ras/ERK and Ras/mTOR pathway in head and neck carcinoma HEp-2 and HSC-3 cells.
Head and neck squamous cell carcinoma (HNSCC) is a major malignancy worldwide. Ras overexpression in HNSCC is known to promote tumor cell growth; therefore, inhibition of Ras activation could lead to tumor growth suppression in HNSCC patients. Here, we investigated the effect of FTI-277, a farnesyl transferase inhibitor, and GGTI-287, a geranyltransferase 1 inhibitor, on the Ras signaling pathway in HNSCC cell lines-HEp-2 and HSC-3. Cell viability was analyzed using the trypan blue staining exclusion assay. The apoptosis of cells was assessed by flow cytometry and caspase activation analysis. The expression levels of proteins were examined using western blot analysis. FTI-277 and GGTI-287 induced cell death, enhanced caspase 3 activity, and increased the number of annexin V-positive cells in HEp-2 and HSC-3 cells. FTI-277 and GGTI-287 induced apoptosis in HSC-3 cells at much lower concentrations than that in HEp-2 cells. FTI-277 and GGTI-287 decreased the concentration of phosphorylated ERK1/2 and mTOR via membrane localization of Ras and enhanced Bim expression. Furthermore, FTI-277 and GGTI-287 induced cell death in v-H-Ras-transfected NIH3T3 (NW7) cells and not in empty vector-transfected NIH3T3 (NV20) cells. FTI-277 and GGTI-287 may be useful as potential therapeutic agents for treating HNSCC patients; moreover, farnesyl transferase and geranylgeranyltransferase 1 inhibitors can be further developed as anticancer agents.


Temperament traits of beef calves measured under field conditions and their relationships to performance.
A total of 3,050 German Angus (Aberdeen Angus x German dual-purpose breeds), Charolais, Hereford, Limousin, and German Simmental calves were used to examine temperament traits of beef cattle using 2 different test procedures. The chute test and the flight-speed test have been validated in terms of routine on-farm applicability. Behavior tests were performed in 2006 and 2007 on 24 commercial beef cattle farms located in the northern and eastern part of Germany. A single, trained observer assigned subjective scores to characterize the behavior of each animal during restraint in the head gate (calm, restless shifting, squirming, vigorous movement, violent struggling) and when leaving the chute (walk, trot, run, jumping out of the chute). Breed was a significant source of variation in chute scores and flight-speed scores (P < 0.001). Charolais and Limousin cattle had the greatest scores in both traits, whereas Herefords had the least (P < 0.001) chute scores. German Angus and Hereford calves had the least (P < 0.001) flight-speeds, indicating that these breeds have a more favorable temperament. Temperament scores differed significantly between male and female calves (P < 0.01), with females scoring better for both traits. Average daily BW gains of the calves were significantly influenced by effects of breed (P < 0.001) and sex (P < 0.001) of the calves. Heritabilities were estimated for chute- and flight-speed scores of beef cattle. They were least for chute score and flight-speed score of Limousin cattle with values of 0.11. In contrast, greatest heritabilities were 0.33 for chute score and 0.36 for flight-speed score of Hereford cattle. Genetic correlations were estimated among both temperament traits, with values between 0.57 and 0.98. Chute scores and visual flight-speed scores were negatively correlated with daily BW gain of the calves in most breeds. The results presented in this paper indicate that on-farm evaluation of beef cattle temperament is possible, either using the chute test or the flight-speed test. Genetic selection seems to be promising to improve temperament traits of beef cattle without decreasing production traits like ADG of the calves.


Binding property of HIV p24 and Reverse transcriptase by chalcones from Pongamia pinnata seeds.
HIV remains a challenging life threatening viral agent for humans despite available anti HIV drugs. The known effective drug named HAART clears the circulating viruses but not the intracellular viruses. Therefore, it is of interest to identify molecules with improved anti-HIV activity from natural plant sources. Hence, we studied the anti-HIV potency of an Indian medicinal plant named Pongamia pinnata. Aqueous extracts were made from leaf, seed and roots of Pongmia pinnata and screened for anti HIV-1 activity using HIV-1 p24 and reverse transcriptase (RT) inhibition assays. Further, the active chalcone derivatives namely, P24 protein and RT enzymes showed promising binding score against Glabarachalcone and Karanijin. Among these extracts, P. pinnta aqueous seed extracts have shown HIV-1 p24 inhibition at 66.9 ± 4.4 percentage. However, RT inhibition assay showed only 36.8%. Hence, the HIV-1 p24 inhibition infers either the prevention of virus entry or inhibits other enzymes and or interferes with virion assembly.


Luteinizing hormone, its beta-subunit variant, and epithelial ovarian cancer: the gonadotropin hypothesis revisited.
The gonadotropin hypothesis postulates that excessive gonadotropin stimulation results in increased proliferation and subsequent malignant transformation of ovarian epithelium. The authors evaluated this hypothesis by analyzing the association between serum levels of wild-type luteinizing hormone (LH) and ovarian cancer risk. They also examined the relation between a variant of LH containing two missense point mutations (Trp(8)Arg and Ile(15)Thr) in its beta-subunit and ovarian cancer risk. Fifty-eight cases of epithelial ovarian cancer and 116 controls matched on age, menopausal status, and date of blood donation were included in a case-control study nested within the New York University Women's Health Study, a prospective cohort enrolled between 1985 and 1991 in New York City. Wild-type serum levels and variant LH status were determined by immunofluorometric assays in which monoclonal antibodies specific for wild-type and variant LH were used. Compared with women in the lowest tertile of wild-type LH, women in the highest tertile had a lower risk of ovarian cancer, after adjustment for potential confounders (odds ratio = 0.42, 95% confidence interval: 0.09, 2.09). Women heterozygous for variant LH were not at increased risk (adjusted odds ratio = 0.95, 95% confidence interval: 0.27, 3.34). The results suggest that neither wild-type LH levels nor variant LH status is associated with increased risk of epithelial ovarian cancer.


[Effects of ferulic acid on the expressions of nephrin and podocin in podocytes of diabetic rats].
To investigate the effects of ferulic acid (FA) on the streptozocin (STZ) -induced kidney injury in diabetic rats and its possible mechanisms. Diabetes was induced in male SD rats by an injection of STZ (40 mg/kg,i.v.). After 72 hours, blood glucose levels were detected and blood glucose levels exceeded 16.7 mmol/L were diagnosed as diabetic model rats. Diabetic model rats were randomly divided into model group and FA group, ten animal in each group. Another 10 healthy male SD rats were treated as control group. The rats in FA group were treated with FA (100 mg/kg, i.g.,qd) from the 5th week since the diabetic rats model was successfully established and lasted for 8 weeks. The levels of blood glucose, body weight, organ coefficient of kidney, blood urea nitrogen and creatinine were tested. HE staining was employed to observe the pathological changes of the renal tissue. Immunohistochemistry was employed to determine the protein of nephrin and podocin. Compared to control group, the levels of blood glucose, organ coefficient of kidney, blood urea nitrogen(BUN) and serum creatinine(sCr) were increased significantly. Renal cells from model group rats showed atrophied and disordered after HE staining and interstitial proliferation were also appeared in renal tissue of the model group. Meantime, the levels of nephrin and podocin protein were obviously decreased. These changes were significantly attenuated in the model group treated with FA. FA can evidently ameliorate renal damage in rats with diabetic nephropathy induced by STZ, which might be related to increase the level of nephrin and podocin protein.


Dimensional changes of one-piece frameworks cast from titanium, base metal, or noble metal alloys and supported on telescopic crowns.
The dimensional accuracy of 1-piece frameworks cast from commercially pure titanium and used to accommodate supporting telescopic crowns has not been demonstrated. To compare dimensional changes incurred in frameworks cast from commercially pure titanium, a cobalt-chromium alloy, and a noble metal (gold) alloy. This study was based on 2 different models, both prepared to receive telescopic crowns: 1 with 4 dies, designed to measure dimensional changes of the castings in the horizontal plane; and another with 2 dies, designed to measure dimensional changes in the vertical plane. As variables for the 2-die models, the palatal shape (16- and 20-mm radius) as well as the palatal depth (20-mm radius with the smallest palatal depth of 8 mm, 16-mm radius with flat palate and palatal depth of 10 mm, 16-mm radius with greatest palatal depth of 16 mm) were studied. Ten specimens each were fabricated from a commercially pure titanium, a cobalt-chromium alloy, and a gold alloy. All castings were fabricated under standardized conditions. All measurements were taken with a computer-controlled measuring microscope at the margins of the simulated telescopic crowns; these served to calculate the ideal midpoint from which the distances between the telescopic crowns were measured. The positional relation of the telescopic crowns was determined in horizontal and vertical directions. The measurements of the cast models were compared with measurements of the original model. The distances between the dies and the angles of the chosen telescopic crowns were calculated in fractions of millimeters and the angles were measured in degrees. The Kruskal-Wallis test and the Mann-Whitney U test were used for statistical analysis. The level of significance was alpha=5%. With the following exceptions, none of the 3 alloy types showed significantly different results. With the 4-die model, all 3 alloys showed significant variations from the original model for chosen lengths (P=.001). For those lengths, the dimensional accuracy of the noble metal alloy was approximately 99.9% of the length of the original; for the 2 other alloys, an average value of 99.4% was determined. With the 2-die models the calculated angle was significantly different from the original model for all alloys (P=.001 or.000), independent from the palatal vault and depth. Significant differences from the original model were also found for the distance between the 2 telescopic crowns with all alloys for the 2-die model with a 16-mm depth palatal vault and a 16-mm radius (P=.001,.006, or.009). Within the limitations of this study, the significant different dimensional changes both for the 4-die models and the 2-die models did not depend on the type of alloy. The 2-die models demonstrated significant dimensional changes resulting from the palatal geometry of the corresponding test models; the 4-die models demonstrated a tendency to contract toward the geometric center.


Tuning the optical and electronic properties of 4,8-disubstituted benzobisoxazoles via alkyne substitution.
In an effort to design new electron-deficient building blocks for the synthesis of conjugated materials, a series of new trans-benzobisoxazoles bearing halogen or alkynyl substituents at the 4,8-positions was synthesized. Additionally, the impact of these modifications on the optical and electronic properties was investigated. Theoretical calculations predicted that the incorporation of various alkynes can be used to tune the energy levels and band gaps of these small molecules. The targeted 4,8-disubstituted benzobisoxazoles were easily prepared in good yields using a two-step reaction sequence: Lewis acid catalyzed orthoester cyclization followed by Sonogashira cross-coupling. The experimentally determined HOMO values for these 4,8-disubstituted benzobisoxazoles ranged from -4.97 to -6.20 eV and showed reasonable correlation to the theoretically predicted values, with a percent deviation that ranged from 2.4-12.8%. However, the deviation between actual and predicted HOMO values was reduced to less than 3.5% when the theoretical values were extrapolated to the long-chain limit and compared to copolymers containing the 4,8-disubstituted benzobisoxazoles. Collectively, these results indicate that these 4,8-disubstituted trans-benzobisoxazoles can be used for the synthesis of new conjugated materials with electronic properties that are variable and predictable.


Importance of evaluating all vascular phases on contrast-enhanced sonography in the differentiation of benign from malignant focal liver lesions.
Our objective was to evaluate the accuracy of a blood-pool sonographic contrast agent in the late phase compared with the three vascular phases for differentiation between benign and malignant focal liver lesions. In 152 patients (105 with chronic liver disease), 152 solid focal liver lesions characterized either by fine-needle biopsy or by dynamic CT or MRI were studied. The final diagnoses were metastasis for 24, hepatocellular carcinoma for 75, focal nodular hyperplasia for 13, regenerating or dysplastic nodule for 14, hemangioma for 22, cholangiocarcinoma for two, and another focal liver lesion for two. Real-time sonography was performed after a bolus injection of 2.4 mL of SonoVue, using a low mechanical index (< 0.2). All lesions were evaluated in the arterial, portal, and late phases; classified as benign or malignant; and correlated with final diagnoses. For discrimination between malignant and benign focal liver lesions, evaluation of all vascular phases improved the sensitivity from 78.4% to 98% and the accuracy from 80.9% to 92.7%, compared with evaluation of the late phase alone. The increase in accuracy was higher in patients with chronic liver disease (16.3%) than in those without (2.1%). Evaluation of SonoVue enhancement in all three vascular phases is superior to evaluation of SonoVue enhancement in the late phase alone, especially in patients with chronic liver disease.


Bilateral axillary metastasis from a primary ethmoidal squamous cell carcinoma.
The development of infra-clavicular lymph node metastasis from head and neck squamous cell carcinoma is an uncommon event. We present a rare case of bilateral axillary nodal metastasis that developed in a patient previously treated for a primary ethmoidal squamous cell carcinoma. To our knowledge, there have only been five case reports in the English literature, accounting for a total of 10 patients, which documented a clinically apparent metastasis to axillary lymph nodes from various head and neck malignancies. Significantly however, the simultaneous ipsilateral and contralateral lymphatic spread of disease from a tumour in the para-nasal sinus, so as to involve bi-axillary nodes, has not been previously reported. We discuss the possible pathogenesis and the prognostic significance of this manifestation.


Dietary Riboflavin Requirement of Pacific White Shrimp (Litopenaeus vannamei).
This study was conducted to determine the dietary riboflavin requirement and its effects on growth performance, feed utilization, innate immunity, and diet digestibility of Litopenaeus vannamei. A riboflavin-free basal diet (R0) was formulated as a control, and six other diets were prepared by adding riboflavin of 10, 20, 30, 40, 50, and 60 mg/kg to the basal diet (designated as R10, R20, R30, R40, R50, and R60, respectively). Quadruplicate groups of shrimp (initial average weight 0.17 ± 0.00 g) were fed the diets six times a day for 8 weeks. Weight gain, specific growth rate, and protein efficiency ratio were significantly increased by riboflavin (p < 0.05). The maximum values were observed in shrimp fed R40 diet. The highest activities of phenoloxidase, nitro blue tetrazolium, superoxide dismutase, and glutathione peroxidase were observed in shrimp fed R40 diet. Lysozyme activity was significantly higher in shrimp fed R30 and R40 diets than that of shrimp fed R60 diet (p < 0.05). Intestinal villi were significantly longer in shrimp fed R50 and R60 diets compared to those of all other groups while the shortest villi were observed in R0 group (p < 0.05). Intestinal villi were clearly distinguished in shrimp fed higher levels of riboflavin compared to those of shrimp fed R0 and R10 diets. Apparent digestibility coefficients of dry matter and protein in diets were not significantly affected by riboflavin levels (p < 0.05). Whole-body proximate composition and hemolymph biochemical parameters were not significantly altered by dietary riboflavin (p < 0.05). Therefore, the results of this study indicate that riboflavin is essential to enhance growth performance, feed utilization, nonspecific immunity, and intestine morphology of shrimp. An optimal riboflavin requirement for the maximum growth of L. vannamei seems to be approximately 40.9 mg/kg diet.


Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma.
The diagnosis of HPV-related oropharyngeal cancer in clinical practice is based on p16 immunohistochemistry and PCR detection of viral DNA (HPV-PCR). The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was to study the clinical characteristics of these patients. This single-centre prospective study was conducted between February 2010 and July 2012. Immunohistochemical analysis of p16 and HPV-PCR were performed on tumour biopsies. Concordance was evaluated according to Cohen's kappa coefficient and was interpreted according to the Landis and Koch scale. The patients' clinical data were analysed as a function of the diagnostic test results. Seventy-one patients were included in this study. The prevalence of HPV was 43.7% according to p16 and 31% according to HPV-PCR. The concordance study revealed a kappa coefficient of 0.615. A tumour of the tonsil or base of the tongue was detected in 100% of p16+/HPV-PCR+ cases. Smoking and alcohol abuse were significantly less frequent among HPV+ patients regardless of the method of detection. These patients were older and presented tumours with a lower grade of histological differentiation. p16 immunohistochemistry or HPV-PCR used alone appear to be insufficient. These results confirm the high prevalence of HPV-related oropharyngeal squamous cell carcinoma (OSCC) and the previously reported specific clinical and histological features, apart from age. It appears essential for future clinical trials to be stratified according to smoking and tumour HPV status, defined by means of reliable virological tests targeting E6/E7 mRNA and no longer a simple positive response to the p16 marker, as is frequently the case at the present time. New tests suitable for use in routine practice therefore need to be developed.


Ferruginol Diterpenoid Selectively Inhibits Human Thyroid Cancer Growth by Inducing Mitochondrial Dependent Apoptosis, Endogenous Reactive Oxygen Species (ROS) Production, Mitochondrial Membrane Potential Loss and Suppression of Mitogen-Activated Protein Kinase (MAPK) and PI3K/AKT Signaling Pathways.
BACKGROUND Thyroid cancer causes considerable mortality and morbidity across the globe. Owing to the unavailability of biomarkers and the adverse effects of existing drugs, there is an urgent need to develop efficient chemotherapy for the treatment of thyroid cancers. Plants have served as exceptional source of drugs for the treatment of lethal diseases. The purpose of this study was to evaluate the anticancer effects of ferruginol against thyroid cancer cells. MATERIAL AND METHODS We monitored the cell proliferation rate using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected using 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB), and annexin V/propidium iodide (PI) staining. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) levels were examined by fluorescence microscopy. Protein expressed was examined by western blotting. RESULTS We found that ferruginol exerted potent antiproliferative action against thyroid cancer cells, and an IC₅₀ of 12 µM was observed for ferruginol against the MDA-T32 cell line. The toxic effects of ferruginol were less pronounced against normal cells. The anticancer effects of ferruginol were likely due to the induction of apoptosis which was also associated with upregulation of Bax and downregulation of Bcl-2. Ferruginol also caused ROS mediated alterations in the MMP of MDA-T32 cells. In MDA-T32 cells, ferruginol might also block the MAPK and PI3K/AKT signaling pathway, which is believed to be an important therapeutic target of anticancer drugs. CONCLUSIONS In conclusion, in view of the results of this study, it might be suggested that ferruginol might serve as an essential lead molecule for the treatment of thyroid cancer provided further in-depth studies especially studying ferruginol toxicological as well as in vivo studies are needed.


Mac-2 binding protein is a novel E-selectin ligand expressed by breast cancer cells.
Hematogenous metastasis involves the adhesion of circulating tumor cells to vascular endothelium of the secondary site. We hypothesized that breast cancer cell adhesion is mediated by interaction of endothelial E-selectin with its glycoprotein counter-receptor(s) expressed on breast cancer cells. At a hematogenous wall shear rate, ZR-75-1 breast cancer cells specifically adhered to E-selectin expressing human umbilical vein endothelial cells when tested in parallel plate flow chamber adhesion assays. Consistent with their E-selectin ligand activity, ZR-75-1 cells expressed flow cytometrically detectable epitopes of HECA-452 mAb, which recognizes high efficiency E-selectin ligands typified by sialofucosylated moieties. Multiple E-selectin reactive proteins expressed by ZR-75-1 cells were revealed by immunoprecipitation with E-selectin chimera (E-Ig chimera) followed by Western blotting. Mass spectrometry analysis of the 72 kDa protein, which exhibited the most prominent E-selectin ligand activity, corresponded to Mac-2 binding protein (Mac-2BP), a heretofore unidentified E-selectin ligand. Immunoprecipitated Mac-2BP expressed sialofucosylated epitopes and possessed E-selectin ligand activity when tested by Western blot analysis using HECA-452 mAb and E-Ig chimera, respectively, demonstrating that Mac-2BP is a novel high efficiency E-selectin ligand. Furthermore, silencing the expression of Mac-2BP from ZR-75-1 cells by shRNA markedly reduced their adhesion to E-selectin expressing cells under physiological flow conditions, confirming the functional E-selectin ligand activity of Mac-2BP on intact cells. In addition to ZR-75-1 cells, several other E-selectin ligand positive breast cancer cell lines expressed Mac-2BP as detected by Western blot and flow cytometry, suggesting that Mac-2BP may be an E-selectin ligand in a variety of breast cancer types. Further, invasive breast carcinoma tissue showed co-localized expression of Mac-2BP and HECA-452 antigens by fluorescence microscopy, underscoring the possible role of Mac-2BP as an E-selectin ligand. In summary, breast cancer cells express Mac-2BP as a novel E-selectin ligand, potentially revealing a new prognostic and therapeutic target for breast cancer.


Surface-polymer stabilized liquid crystals with dual-frequency control.
Dual-frequency control liquid crystal (LC) and thin reactive mesogen (RM) films, cast on internal surfaces of cell substrate, are used to build surface polymer stabilized structures. Electric field of high frequency is used to orient the LC molecules by the negative dielectric torque prior to the photopolymerization of RM films. Electro-optic characterization results show that the contrasts of light scatter modulation and polarization dependence are noticeably improved by the dual-frequency control. However, there is no significant shortening in the full cycle duration of excitation-relaxation-excitation.


Molecular genetic analysis of six Dutch families with atrial fibrillation.
Atrial fibrillation (AF), the most common cardiac arrhythmia, is characterised by rapid and irregular contraction of the atrium. The risk of AF increases with age and AF increases the risk of various heart disorders, stroke and mortality. AF can occur in a sporadic or familial form. The underlying mechanism leading to AF is not well known but genetic analysis can increase our insight into the molecular pathways in AF. Detailed information on the molecular mechanisms of a disorder increase options for diagnosis and treatment. Recently, a gain-of-function mutation in exon of the KCNQ1 gene located on chromosome 11 was identified in a large Chinese AF family. KCNQ1 associates with KCNE1 or KCNE2 (both located on chromosome 21) to form cardiac potassium channels. Subsequent analysis of Chinese families showed a KCNE2 mutation in two families. Other genetic studies show linkage to chromosome 6 and 10, indicating genetic heterogeneity. A number of studies have shown that altered expression of the atrial connexin40 protein is a risk factor for AF. Connexin genes encode gap-junction proteins that are important in cardiac conduction and for normal wave propagation. In this study we analysed the role of KCNQ1, KCNE1 coding region and Cx40 promoter region in six Dutch AF families by sequence analysis. No mutations were found in these genes. The absence of mutations indicates genetic heterogeneity in familial AF; however, further research is needed. Candidate genes are being sequenced, linkage analysis in a large family will be performed and additional AF families will be collected.


Osteoporosis and fractures: the size of the problem.
The public health impact of osteoporosis-related fractures is enormous, with important economic implications. Government agencies and health-care providers must recognize the importance of early diagnosis of osteoporosis, implement policies for the prevention of disease, and develop effective payment policies for densitometry examinations.


Pilot study of Alteplase (tissue plasminogen activator) for treatment of urinary clot retention in an in vitro model.
The management of urinary clot retention and hematuria involves manual irrigation with sterile water or normal saline via a Foley catheter followed by continuous bladder irrigation. Irrigation may become difficult because of the formation of dense blood clots. Tissue plasminogen activator (t-PA/Alteplase) may be a useful pharmacological agent to improve the efficacy of manual irrigation of large, dense clots. The goal of the current study was to compare t-PA to sterile water for clot irrigation in an in vitro model. In vitro models of clot retention were created using 500-cc urinary leg bags each filled with 80 cc of unpreserved whole blood from a healthy volunteer. Each model was incubated at 25 degrees C for 24 hours to allow clot formation. Four models each with 25 mL solution of t-PA at concentrations of 2, 1, 0.5, and 0.25 mg/mL were evaluated and compared to a control (25 mL sterile water). Models were instilled with solution (t-PA or control) and incubated for 30 minutes at 37 degrees C, and then irrigated with sterile water via 18F Foley by a blinded investigator. Three separate experiments were conducted, and statistical analysis was performed comparing various irrigation parameters. Clot evacuation with 25 mL of t-PA at a concentration of 2 mg/mL (50 mg) was significantly easier (p = 0.05) and faster (p < 0.05) than the sterile water control. The mean time for clot evacuation in this model was 2.7 minutes for t-PA solution 2 mg/mL versus 7.3 minutes for the control (p < 0.05). Compared to the control, irrigation with t-PA solution 2 mg/mL also required less irrigant (180 mL vs. 500 mL) (p < 0.05) for complete evacuation. There was a similar trend in efficacy for the lower doses of t-PA, but this was not statistically significant. In this in vitro study, a single 25 mL instillation of t-PA solution 2 mg/mL is significantly better than sterile water alone for clot evacuation. In vivo animal studies are pending.


IL-27 imparts immunoregulatory function to human NK cell subsets.
Interleukin-27 (IL-27) is a cytokine with multiple roles in regulating the immune response, but its effect on human CD56(bright) and CD56(dim) NK cell subsets is unknown. NK cell subsets interact with other components of the immune system, leading to cytotoxicity or immunoregulation depending on stimulating factors. We found that IL-27 treatment results in increased IL-10 and IFN-γ expression, increased viability and decreased proliferation in both CD56(bright) and CD56(dim) NK cell subsets. More importantly, IL-27 treatment imparts regulatory activity to CD56(bright) NK cells, which mediates its suppressive function on T cells in a contact-dependent manner. There is growing evidence that CD56(bright) NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. Thus, understanding the role of IL-27 in NK cell function has important implications for treatment of autoimmune disorders.


Optics and pathology.
The Armed Forces Institute of Pathology is a triservice organization engaged in consultation, education, and research in pathology in support of the armed services and in cooperation with other governmental agencies and with civilian medicine. References are given to publications of members of the Institute staff, principally in the areas of light and electron microscopy (including optical cytochemical methods and quantitative electron microscopy), spectrophotometry, x-ray diffraction, x-ray fluorescence, and laser studies.


Copper Amine Oxidase (CuAO)-Mediated Polyamine Catabolism Plays Potential Roles in Sweet Cherry (Prunus avium L.) Fruit Development and Ripening.
Copper amine oxidases (CuAOs) play important roles in PA catabolism, plant growth and development, and abiotic stress response. In order to better understand how PA affects cherry fruit, four potential PavCuAO genes (PavCuAO1-PavCuAO4) that are dispersed over two chromosomes were identified in the sweet cherry genome. Based on phylogenetic analysis, they were classified into three subclasses. RNA-seq analysis showed that the PavCuAO genes were tissue-specific and mostly highly expressed in flowers and young leaves. Many cis-elements associated with phytohormones and stress responses were predicted in the 2 kb upstream region of the promoter. The PavCuAOs transcript levels were increased in response to abscisic acid (ABA) and gibberellin 3 (GA3) treatments, as well as abiotic stresses (NaCl, PEG, and cold). Quantitative fluorescence analysis and high-performance liquid chromatography confirmed that the Put content fell, and the PavCuAO4 mRNA level rose as the sweet cherry fruit ripened. After genetically transforming Arabidopsis with PavCuAO4, the Put content in transgenic plants decreased significantly, and the expression of the ABA synthesis gene NCED was also significantly increased. At the same time, excessive H2O2 was produced in PavCuAO4 transiently expressed tobacco leaves. The above results strongly proved that PavCuAO4 can decompose Put and may promote fruit ripening by increasing the content of ABA and H2O2 while suppressing total free PA levels in the fruit.


Reuse of EHRs to Support Clinical Research in a Hospital of Reference.
Most hospitals have already implemented information systems and Electronic Health Records (EHRs), but the reuse of such data for research is still infrequent. We present a pilot project on the exploitation of clinical information from a Spanish hospital database in the context of the European Medical Information Framework project (EMIF). Specific use cases such as patients with diabetes mellitus type 2, obesity and dementia were assessed, by exploiting EHR data integrated from several separated clinical databases. The possibility to analyse the features of specific groups of patients based on their diagnosis codes can provide new data about relationships between different conditions that can contribute for decision-making, healthcare and research.


Reverse breeding: a novel breeding approach based on engineered meiosis.
Reverse breeding (RB) is a novel plant breeding technique designed to directly produce parental lines for any heterozygous plant, one of the most sought after goals in plant breeding. RB generates perfectly complementing homozygous parental lines through engineered meiosis. The method is based on reducing genetic recombination in the selected heterozygote by eliminating meiotic crossing over. Male or female spores obtained from such plants contain combinations of non-recombinant parental chromosomes which can be cultured in vitro to generate homozygous doubled haploid plants (DHs). From these DHs, complementary parents can be selected and used to reconstitute the heterozygote in perpetuity. Since the fixation of unknown heterozygous genotypes is impossible in traditional plant breeding, RB could fundamentally change future plant breeding. In this review, we discuss various other applications of RB, including breeding per chromosome.


Germany: Health System Review.
This analysis of the German health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. Germany's health care system is often regarded as one of the best health care systems in the world, offering its population universal health insurance coverage and a comprehensive benefits basket with comparably low cost-sharing requirements. It provides good access to care with free choice of provider and short waiting times, which is partly due to good infrastructure with a dense network of ambulatory care physicians and hospitals, and a quantitatively high level of service provision. With the largest economy in the EU it is not surprising that Germany spends more than other countries on health, with most financing coming from public funds. The country had the highest per capita spending in the EU in 2018. In relation to overall health expenditure and available resources, a very high number of services is provided across sectors, particularly in hospital and ambulatory care. This can be seen as achieving a considerable level of technical efficiency. Given the high volumes, however, there are questions about the oversupply of services, as well as some comparatively moderate health and quality outcomes; from this perspective, there are signs that there is room for improvement in how the system allocates resources. Additional challenges in the German health system may be identified in: (1) the strong separation of ambulatory and inpatient care in terms of organization and payment, which can hinder the coordination and continuity of patient treatment; (2) the coexistence of statutory health insurance (SHI) and substitutive private health insurance (PHI), which weakens the principle of solidarity; and (3) a complex stewardship framework which promotes incrementalism and makes it more difficult to implement reforms.


Effects of Physical Exercises and Verbal Stimulation on the Functional Efficiency and Use of Free Time in an Older Population under Institutional Care: A Randomized Controlled Trial.
Older people in institutional care are, for the most part, physically inactive and do not interact with each other or medical staff. Therefore, reducing sedentary behaviour is a new, important, and modifiable lifestyle variable that can improve the health of elderly people. The aim of the project was to assess the degree of improvement in functional performance and the possibility of changing habitual, free time behaviour among elderly people under institutional care by applying physical training with verbal stimulation. The study covered older people, aged 65-85 years, who are living a sedentary lifestyle in care homes in Southeastern Poland. Those who met the eligibility criteria were enrolled in the study and were assigned, at random, to one of four parallel groups: basic exercises (n = 51), basic exercises combined with verbal stimulation (n = 51), functional exercise training (n = 51), and functional exercise training with verbal stimulation (n = 51). No statistically significant differences in baseline characteristics were observed across the groups. Data were collected at baseline and at 12 and 24-weeks following the completion of the intervention. In the group with functional exercise training with verbal stimulation, in comparison to the group with basic exercises, the greatest positive short-term impact of intervention was demonstrated in terms of functional fitness (increased by 1.31 points; 95% confidence interval (CI) = 0.93-1.70), gait speed (improved by 0.17 m/s, 95% CI = 0.13-0.22), hand grip strength (by over 4 kg; 95% CI = 2.51-4.95), and upper-limb flexibility (by 10 cm; 95% CI = 5.82-12.65). There was also a significant increase in the level of free-time physical activity and an improvement in the quality of life, especially as expressed in the domain of overall physical functioning. Our study showed that a functional exercise program, combined with verbal stimulation, is effective at improving physical fitness and raising the level of free-time physical activity.


Church-based social support and health in old age: exploring variations by race.
A conceptual model is evaluated that explores the relationship between church-based support and health. In the process, an effort is made to see if the relationships in this model differ for older White and African American people. Interviews were conducted with a national sample of 748 older White and 752 older Black people. The responses of 1,126 of these study participants are used in the analyses presented herein. Survey measures were administered to assess church-based social ties and health. Empirical support was provided for the following theoretical linkages: Older people who attend church often feel their congregations are more cohesive; older people in highly cohesive congregations receive more spiritual and emotional support from their fellow parishioners; older respondents who receive more church-based support have a more personal relationship with God; older people who feel more closely connected with God are more optimistic; and older people who are more optimistic enjoy better health. Data further reveal that older Black people are more likely than older White people to reap the health-related benefits of religion. The findings contribute to research on religion and health by specifying how the salubrious effects of religion may arise.


LONGITUDINAL STUDY OF CHANGES IN INNER SCLERAL CURVATURE PATTERNS AND DEVELOPMENT OF POSTERIOR STAPHYLOMAS IN HIGHLY MYOPIC EYES OF CHILDREN AND ADOLESCENTS.
To determine the longitudinal changes in patterns of inner scleral curvature and development of posterior staphylomas in the eyes of highly myopic youths. A retrospective, longitudinal study. Ultra-widefield optic coherence tomographic (UWF-OCT) images from 47 eyes of 24 highly myopic patients with a follow-up period of 2 to 4 years were analyzed. Patients were divided into two groups, the children group younger than 10 years and the adolescents group aged 11 to 19 years. During the follow-up period, the scleral curvature patterns changed in either the horizontal or vertical optical coherence tomographic sections in 27 of the 46 eyes (58.7%) of both groups. The changes were significantly more frequent in children than adolescents. The change in the vertical section from symmetrical to asymmetrical in almost of children was correlated with an increase in the axial length and myopia. Four eyes had a staphyloma at the baseline. The staphyloma developed in six eyes of the remaining 43 eyes (14%). All staphyloma edges were found at or around the optic disc and were oriented in the horizontal direction. Our results showed that UWF-OCT images can be used to determine the process of new staphyloma formation and concurrent changes in scleral curvature patterns.


On the origin of altered diastereomeric ratios for anionic versus neutral reaction conditions in the oxy-Cope/ene reaction: an interplay of experiment and computational modeling.
We report herein a detailed investigation into the reaction mechanism for a sequential oxy-Cope/ene reaction under anionic conditions. With DFT calculations and ab initio molecular dynamics simulations, the observed diastereoselectivity is shown to be the result of an isomerization of the enolate olefin, which would evidently not occur under neutral conditions. The potential energy surface was thoroughly mapped out for the reaction pathways and the proposed mechanism confirmed the different product distributions observed under neutral and anionic oxy-Cope conditions. In addition, other possible pathways are shown to be higher in energy and experimental evidence is given that supports the olefin-isomerization pathway.


Kinetics and quantitative structure-activity relationship study on the degradation reaction from perfluorooctanoic acid to trifluoroacetic acid.
Investigation of the degradation kinetics of perfluorooctanoic acid (PFOA) has been carried out to calculate rate constants of the main elementary reactions using the multichannel Rice-Ramsperger-Kassel-Marcus theory and canonical variational transition state theory with small-curvature tunneling correction over a temperature range of 200~500 K. The Arrhenius equations of rate constants of elementary reactions are fitted. The decarboxylation is role step in the degradation mechanism of PFOA. For the perfluorinated carboxylic acids from perfluorooctanoic acid to trifluoroacetic acid, the quantitative structure-activity relationship of the decarboxylation was analyzed with the genetic function approximation method and the structure-activity model was constructed. The main parameters governing rate constants of the decarboxylation reaction from the eight-carbon chain to the two-carbon chain were obtained. As the structure-activity model shows, the bond length and energy of C1-C2 (RC1-C2 and EC1-C2) are positively correlated to rate constants, while the volume (V), the energy difference between EHOMO and ELUMO (ΔE), and the net atomic charges on atom C2 (QC2) are negatively correlated.


Effect of gender composition of school on body concerns in adolescent women.
This study aimed to investigate the role of gender composition of school on body figure preferences, eating disorder symptomology, and role concerns. Questionnaires were completed by 261 Australian adolescent girls in two private single-sex and two private coeducational school environments. There was no difference in nominated ideal figure or eating disorder scores between the schools. However, girls in the single-sex schools placed a greater emphasis on achievement than their counterparts at the coeducational schools. These role concerns had a differential impact on prediction of the ideal figure, whereby the importance placed on intelligence and professional success predicted the choice of a thinner ideal figure for the single-sex schools, but a larger ideal for the coeducational schools. It was concluded that the motivation for thinness differs between single-sex and coeducational schools.


Managing common nail disorders in active patients and athletes.
Sports-related acute nail trauma can cause subungual hematoma and pain, which can be alleviated by fluid evacuation; the differential diagnosis includes subungual melanoma. A careful history will help distinguish splinter hemorrhages related to systemic disease from those caused by trauma. Chronic trauma can damage the nail matrix, leading to longitudinal splits or ridging, pigmentary changes, pterygium, or dystrophy. Mildly ingrown toenails can be treated with cotton placed under the lateral nail edges and proper trimming; severe cases may require surgery. Treatment of acute paronychia includes systemic antibiotics, while chronic paronychia may require topical or systemic antifungal agents.


Complications in reverse total shoulder arthroplasty.
Reverse total shoulder arthroplasty was initially used to manage complex shoulder problems. Indications have been expanded to include rotator cuff arthropathy, massive rotator cuff tear, failed shoulder arthroplasty, and fracture sequelae. Increased use of primary reverse total shoulder arthroplasty has led to reports of associated problems unique to the procedure. The most common complications include neurologic injury, periprosthetic fracture, hematoma, infection, scapular notching, dislocation, mechanical baseplate failure, and acromial fracture. Little information has been published regarding best practices for managing these complications.


Multitargeting: An Alternative Approach to Tackle Multidrug Resistance in Tuberculosis.
The prevalence of drug-resistant organisms has steadily increased over the past few decades worldwide. Especially in tuberculosis (TB) disease, the problems of co-morbidity and the rapid emergence of multidrug resistance have necessitated the development of multitarget-based therapeutic regimens. Several multitargeting compounds against Mycobacterium tuberculosis (Mtb) have been studied through novel in silico tools but these have rendered reduced efficacy in clinical trials. The authors have focussed on many exotic targets belonging to crucial Mtb survival pathways whose molecular structures and functions are underexplored. Likewise, insights into the hidden possibilities of promiscuous compounds from natural products or repurposed drugs to inhibit other cellular proteins apart from their validated targets are also depicted in this review. In addition to the existing line of drugs currently recommended for multidrug-resistant TB, newer host-directed therapies could also be fruitful. Furthermore, several challenges, including safety/efficacy ratios of multitarget compounds highlighted here, can also be circumnavigated by researchers to design "smart drugs" for improved tuberculosis therapeutics. A holistic approach towards alleviating the existing drawbacks of drug discovery in drug-resistant TB has been outlined. Finally, considering the current needs, the authors have put forward an overall summary of possible trends in multitargeting that are significant for futuristic therapeutic solutions.


Proteogenomic Characterization of Endometrial Carcinoma.
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.


Effects of ion concentrations on the hydroxyl radical scavenging rate and reducing power of fish collagen peptides.
Empirical evidence proves that the antioxidant property plays a main role in the biological activities of biomaterials, which is influenced by several factors. In order to explore in-depth, the influence of ionic systems on the antioxidant activity of collagen peptides was studied. Type-I-collagen peptides (GBB-10SP and TYPE-S) contained a high amount of hydrophobic amino acids and possessed good antioxidant activity at high concentrations in water. On the other hand, increasing [H+ ] and [Na+ ] concentrations (0.1 M to 0.5 M) decreased the reducing power of GBB-10SP and TYPE-S; however, [Ca2+ ] had no effect on the reducing power. Interestingly, the hydroxyl radical scavenging rate of these two peptides was increased by [Na+ ], decreased by [H+ ], and [Ca2+ ] had no effect. In general, TYPE-S showed better antioxidant properties than GBB-10SP. Overall, the above results confirmed that the antioxidant capacity of collagen peptides was affected by [H+ ] and [Na+ ] and not by [Ca2+ ]. PRACTICAL APPLICATIONS: The present study mainly deals with the influence of ions on the antioxidant properties of collagen peptides. Recently, fish collagen peptides have been widely used as food supplements to cure several disorders and maintain normal physiological health in humans. It is noted that the use of collagen from fish processing wastes has brought several potential benefits including low value-added products, preventing environmental pollution, and disease transmission by mammalian-based collagen. But the biological activity of this peptide varied based on the preparation and its biochemical compositions. Here, we are reporting how to improve the biological activity of collagen, and also the factors affecting the antioxidant properties in order to avoid the down-regulating mechanism. This study concluded that the [H+ ] and [Na+ ] influenced the antioxidant properties of collagen peptides, but [Ca2+ ] had not effect on the antioxidant properties.


Molecular genetics and treatment of narcolepsy.
Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy. The hypocretin/orexin deficiency is likely to be the key to its pathophysiology in most of cases although the cause of human narcolepsy remains elusive. Acting on a specific genetic background, an autoimmune process targeting hypocretin neurons in response to yet unknown environmental factors is the most probable hypothesis in most cases of human narcolepsy with cataplexy. Although narcolepsy presents one of the tightest associations with a specific human leukocyte antigen (HLA) (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility. In addition to a point mutation in the prepro-hypocretin gene discovered in an atypical case, a few polymorphisms in monoaminergic and immune-related genes have been reported associated with narcolepsy. The treatment of narcolepsy has evolved significantly over the last few years. Available treatments include stimulants for hypersomnia with the quite recent widespread use of modafinil, antidepressants for cataplexy, and gamma-hydroxybutyrate for both symptoms. Recent pilot open trials with intravenous immunoglobulins appear an effective treatment of cataplexy if applied at early stages of narcolepsy. Finally, the discovery of hypocretin deficiency might open up new treatment perspectives.


Experimental Cholera in Chinchillas: the Immune Response in Serum and Intestinal Secretions to Vibrio cholerae and Cholera Toxin.
The immune response to Vibrio cholerae and cholera toxin was studied in chinchillas inoculated intra-intestinally with 10(8) viable V. cholerae 596B. Sera and intestinal fluids were collected from animals on days 1, 2, 3, 5, 7, 10, 14, 30, and 60 postinoculation, and antibodies were quantified by various methods. When radiovibriolytic and radiotoxin precipitin tests were used, a significant (fourfold) rise in both antibacterial and antitoxic titers was detected in intestinal fluids on the 2nd day of infection. In contrast, a significant rise in serum antibodies occurred between days 3 and 5. Since the acute phase of the chinchilla disease lasts 1 to 3 days, recovery coincided with rise in intestinal antibody but not with rise in serum antibody. Our results indicate that both antibacterial and antitoxic mechanisms are operative in chinchilla cholera and that the initial and crucial immune response is local in nature.


Human testicular cell suspensions in vitro using post mortem material.
A method is described for culturing human testicular cells from post mortem material for at least 10 days in a serum free medium. The success of the technique is based on the fact that a layer of testicular cells remains undisturbed on the bottom of a culture flask during culturing and the medium is constantly renewed by a perfusion flow. It is shown that cells form junctions within several hours allowing metabolic coupling, indicating active survival of cells during culture period.


Continuity of cancer care.
The importance of providing continuity in the care of all patients with major medical problems, such as cancer, has widespread acceptance in our current health care system. From the perspective of an oncology social work clinician, this article offers a definition of the concept of continuity of care, examines factors influencing its provision in oncology, and reviews key components in continuity of cancer care planning and implementation. It also examines some innovative efforts in practice to improve continuity.


The uptake exploration of 68Ga-labeled NGR in well-differentiated hepatocellular carcinoma xenografts: Indication for the new clinical translational of a tracer based on NGR.
18F-FDG has low uptake and poor diagnostic efficiency in hepatocellular carcinoma (HCC), particularly in well-differentiated HCC. The NGR peptide selectively targets CD13, which is overexpressed in many types of tumor cells as well as neovasculature cells. In the present study, we aimed to evaluate the feasibility of utilizing 68Ga-NGR to image CD13-positive well-differentiated HCC xenografts. The in vitro cellular uptake, in vivo micro-PET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well‑differentiated HCC xenografts. The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) xenografts were respectively used as positive and negative reference groups for CD13. The expression of CD13 was qualitatively verified by immunofluorescence staining and immunohistostaining studies. The expression levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by western blotting. The in vitro SMMC-7721 cellular uptake of 68Ga‑NGR was significantly higher than that of 18F-FDG (1.23±0.11 vs. 0.515±0.14%; P<0.01). The in vivo micro-PET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721-derived tumors was 2.17±0.21% ID/g (percentage of injected dose per gram of tissue), which was higher compared to that of 18F-FDG (0.73±0.26% ID/g; P<0.01); however, the tumor/liver ratio of 68Ga-NGR was 2-fold higher than that of 18F-FDG. We concluded that the uptake of 68Ga-NGR was significantly higher both in vitro and in vivo than 18F-FDG in the well‑differentiated HCC xenografts and therefore, it is promising for further clinical translation in well-differentiated HCC PET/CT diagnosis.


[Sexual functioning and information needs in women with premature menopause following breast cancer treatment].
Breast cancer is the most common malignant disease among women in Israel and the western world. Approximately 4,000 women a year are diagnosed with breast cancer in Israel and about 900 die as a result of the disease. Large numbers of women who had breast cancer are struggling to cope with sexually oriented difficulties. They feel ashamed and embarrassed in front of their doctor or nurse regarding what they might think about them, for instance if they dare to ask a question regarding a non life-threatening subject. The aims of this research are: 1. To describe the changes in physiological and sexual function among young Israeli women who survived breast cancer and as a consequence experience premature menopause. 2. To understand their information needs regarding sexual functioning. 3. To examine if and to what extent these needs were met by the professional staff. This research was based on the fact that the professional staff provides the patients with information regarding the surgery, the effects of chemotherapy and nutrition but avoids providing substantial information about predicted altered sexual functions and premature menopause. Research shows that medical staff members ignore this crucial information due to personal, professional and social reasons. In a cross-sectional convenience sample, data was collected from 82 women who had been diagnosed with grade 1-2 breast cancer and were treated by one or more of four interventions: surgery, chemotherapy, radiation and hormonal therapy. They were asked to fill out a four-part self-questionnaire. 1. Premature menopause differs from physiological menopause by the symptom acuteness and intensity. 2. Women treated with chemotherapy reported more sexual function difficulties in comparison to other treatments. 3. Women treated with chemotherapy reported increased sexual pleasure and decreased dyspareunia over time following the completion of treatment. 4. Most women reported no significant influence on their ability to experience orgasm during treatments. 5. Almost all the women received a considerable amount of information about treatments and their side effects, but limited information about sexual function, and were very interested in receiving more information on this subject. Breast cancer is becoming more widespread amongst young women. Therefore, it is very important for the medical staff, despite the difficulties, to prepare women treated for breast cancer for the effects of this treatment on sexual function and premature menopause.


Sequence elements responsible for DNA curvature.
Intrinsic DNA bending or curvature is a phenomenon that has been shown to play an important role in a variety of DNA transactions. Large curvature occurs when short homopolymeric (dA.dT)4-6 runs (A-tracts) are repeated in phase with the helical screw. We have used electrophoretic mobility modulation to examine how bending depends on the nature of the 5 bp DNA sequence between the A tracts in molecules of the form (A5-6N5)n. We show that A-tract-induced DNA curvature can indeed be affected by other sequence elements, although by only about +/- 10%. The small observed curvature modulation implies that the overall helix axis deflection contributed by 5-bp B-DNA segments between A-tracts varies little from one sequence to another. This result validates, to first order, the assumption that DNA curvature results from inserting A-tracts at integral turn phasing into generic B-DNA. Therefore, if, as has been proposed, A-tracts have zero roll between the base-pairs and all curvature results from positive roll in the B-DNA segments, then this must be a general property of approximately 5 bp B-DNA sequences, not just special cases. This interpretation would require that the canonical structure of B-DNA be revised to include systematic roll between the base-pairs of about 6 degrees. Alternatively, the data are also consistent with zero average roll in the B-DNA sequences, and wedge angles dominated by negative roll in the A-tracts, or with an appropriate mixture of the two models. It is not possible to resolve this ambiguity using comparative electrophoresis or existing structural data. We show that published wedge angle parameters successfully predict the measured direction and, with appropriate rescaling, the magnitude of curvature due to a non-A-tract sequence containing the protein-free lac operator CAP protein binding site.


Development of a new production system for weaned and growing pigs.
The design of modem housing systems for farm animals calls for cooperation between scientists within different disciplines. This article describes the design of a new production system for weaned and growing pigs, as well as the analyses and working processes behind its development. The aim of the study was to develop an economically competitive system that also provided better welfare for the animals and a healthier environment for the workers. Analyses were carried out with emphasis on behavioral needs and building design and economy. The resulting system, the "safari system," consists of a number of straw flow pens of increasing size. Pigs are moved to larger and larger pens each week until slaughter. The main advantage is that pigs are not mixed during the growth period and that they are given more space, especially toward the end of the growth period when their space demand is high. Furthermore, the provision of straw for comfort and exploration and of wallow basins for cooling in the pens for the larger pigs were considered significant welfare improvements. An analysis revealed that the safari system would be economically competitive in comparison to traditional intensive systems.


Platelet-rich plasma enhances the proliferation of human adipose stem cells through multiple signaling pathways.
Platelet-rich plasma (PRP) is an autologous blood product that contains a high concentration of several growth factors. Platelet-derived growth factor (PDGF)-BB is a potential mitogen for human adipose-derived stem cells (hASCs). PRP stimulates proliferation of hASCs; however, the signaling pathways activated by PRP remain unclear. hASCs were cultured with or without PRP or PDGF-BB, and proliferation was assessed. hASCs were also treated with PRP or PDGF-BB with or without imatinib, which is a PDGF receptor tyrosine kinase inhibitor, or sorafenib, which is a multikinase inhibitor. Inhibition of cell proliferation was examined using anti-PDGF antibody (Abcam, Cambridge, UK), by cell counting. We assessed the effects of inhibitors of various protein kinases such as ERK1/2, JNK, p38, and Akt on the proliferation of hASCs. The proliferation was remarkably promoted in cells treated with either 1% PRP or 10 ng/ml PDGF-BB, and both imatinib and sorafenib inhibited this proliferation. Anti-PDGF antibody (0.5 and 2 μg/ml) significantly decreased the proliferation of hASCs compared with control. PRP-mediated hASC proliferation was blocked by inhibitors of ERK1/2, Akt, and JNK, but not by an inhibitor of p38. PRP promotes hASC proliferation, and PDGF-BB in PRP plays a major role in inducing the proliferation of hASCs. PRP promotes hASC proliferation via ERK1/2, PI3K/Akt, and JNK signaling pathways.


Effects of resveratrol on NO secretion stimulated by insulin and its dependence on SIRT1 in high glucose cultured endothelial cells.
To investigate the effects of resveratrol on the secretion of NO induced by insulin in high glucose cultured primary human umbilical vein endothelial cells (HUVEC). HUVEC were treated with 1 μmol/l resveratrol for 24 h before cultured in high glucose medium for 48 h, then all cells were stimulated by 100 nmol/l insulin for 30 min. Method based on nitric acid reductase was used to analyze the NO contents in the supernatant. Cells were collected to analyze the expression of eNOS, endothelin-1, E-selectin, and SIRT1. In order to investigate the dependence of resveratrol on SIRT1, the effects of resveratrol on cells treated by SIRT1 siRNA were also examined. Compared with control cells, high glucose decreased the secretion of NO induced by insulin. Resveratrol treatment increased the expression of SIRT1 and the secretion of NO. After interfering the expression of SIRT1 using SIRT1 siRNA, the effects of resveratrol on the NO secretion induced by insulin was impaired. Resveratrol also counteracted other pro-atherosclerotic effects of high glucose, including the up-regulating roles of high glucose on the expression of endothelin-1 mRNA and E-selectin mRNA, and the down-regulating roles of high glucose on the expression of eNOS mRNA and the basal NO secretion without the stimulating of insulin. Resveratrol can improve the NO stimulating function of insulin in high glucose cultured HUVEC in SIRT1-dependent manner. Thus, our results imply that resveratrol may have the preventive roles of atherosclerosis in diabetic patients.


Global patterns of child health: the role of nutrition.
Almost two-thirds of the deaths of children around the world are directly or indirectly associated with nutritional deficiencies. Both protein-energy malnutrition and micronutrient deficiencies increase the risk of death from common diseases such as acute gastroenteritis, pneumonia and measles. Iron deficiency anemia is estimated to affect almost 25% of the world's population (equivalent to 3.5 billion people) resulting in high economic costs by adding to the burden on healthcare services, affecting learning in school and reducing adult productivity. Dietary practices frequently seen in older children and adolescents from industrialized countries, leading to frequent consumption of often nutrient-poor foods, may also put them at risk of micronutrient deficiencies. Marginal nutrient deficiencies in the developed world are increasingly accepted as risk factors for the development of chronic disease such as cardiovascular disease or some cancers.


[Postoperative patient controlled analgesia].
Patient controlled analgesia (PCA) helps patients to achieve a better comfort both at rest and when dynamic pain is concerned. This aim can be reached by closing the feedback loop in a shorter time. The purpose is to keep drug concentration in the narrow therapeutic range of MEAC (minimal effective analgesic concentration). Two methods of administration can be used: demand bolus; continuous infusion rate plus demand bolus. Continuous infusion method together with opioids administration increases lethal complications 0.28 to 1.08% (p<0.05), unless patient controlled epidural analgesia (PCEA) is performed. Therefore, this method can be used only in ICU environment. An effective and safe dose delivering and a correct infusion timing is now possible due to recent improvement in technology. The success in PCA depends more by parameters chosen, patient and healthcare personnel compliance, monitoring of S(p)O(2), respiratory rate, pain VAS and Sedation Score than by the drug administered. There is recent evidence that PCA improves patient's comfort, but does not reduce the amount of personnel work, postoperative morbidity, analgesic consumption and costs.


Where does the Occluded Artery Trial leave the late open artery hypothesis?
As of April 2007 the early open artery hypothesis is alive and well, but the late open artery hypothesis is adrift. For the foreseeable future, stable patients with persistent occlusion of the infarct artery late after myocardial infarction, and without severe ischaemia or uncontrollable angina, should be managed initially with optimal medical treatment alone, and not with percutaneous coronary intervention. Efforts should focus on establishing reperfusion earlier, including reducing the time to patient presentation.


An actinomycete strain of Nocardiopsis lucentensis reduces arsenic toxicity in barley and maize.
Accumulation of arsenic in plant tissues poses a substantial threat to global crop yields. The use of plant growth-promoting bacterial strains to mitigate heavy metal toxicity has been illustrated before. However, its potential to reduce plant arsenic uptake and toxicity has not been investigated to date. Here, we describe the identification and characterization of a Nocardiopsis lucentensis strain isolated from heavy metal contaminated soil. Inoculation with this bioactive actinomycete strain decreased arsenic root and shoot bioaccumulation in both C3 and C4 crop species namely barley and maize. Upon arsenate treatment, N. lucentensis S5 stimulated root citric acid production and the plant's innate detoxification capacity in a species-specific manner. In addition, this specific strain promoted biomass gain, despite substantial tissue arsenic levels. Detoxification (metallothionein, phytochelatin, glutathione-S-transferase levels) was upregulated in arsenate-exposed shoot and roots, and this response was further enhanced upon S5 supplementation, particularly in barley and maize roots. Compared to barley, maize plants were more tolerant to arsenate-induced oxidative stress (less H2O2 and lipid peroxidation levels). However, barley plants invested more in antioxidative capacity induction (ascorbate-glutathione turnover) to mitigate arsenic oxidative stress, which was strongly enhanced by S5. We quantify and mechanistically discuss the physiological and biochemical basis of N. lucentensis-mediated plant biomass recovery on arsenate polluted soils. Our findings substantiate the potential applicability of a bactoremediation strategy to mitigate arsenic-induced yield loss in crops.


[Progress in the effects of warming on soil N2O and CH4 emission and the underlying micro-bial mechanisms].
Global warming has received widespread concern. The increasing concentration of greenhouse gases (GHG) is one of the major factors contributing to global warming. Soil is a major source of GHG. Global warming could feed back on soil GHG emission. Warming influences the growth of plants, animals, microbes and their interactions, as well as the cycling of soil matters (especially nitrogen and carbon). Consequently, warming has the potential to affect soil GHG emission. We summarized the effects of warming on soil N2O, and CH4 emissions and the underlying mechanisms. In general, warming increased the emission of these two greenhouse gases, which are mainly related to the effects of temperature on the abundance and composition of ammonia oxidizing bacteria, denitrification functional genes, methane-producing bacteria and methane-oxidizing bacteria. Soil GHG emissions are affected by plant species characteristics, nutrient uptake and community composition, as well as soil nutrient element content, water content, pH and other physical and chemical properties. Further studies are needed to elucidate the microbial mechanisms of GHG emission. In addition, various warming patterns should be considered in the study of GHG emissions, and more attention should be paid on the interactive effects between warming and other environmental factors. It will provide solid theoretical basis for the prediction of global climate change and GHG emissions.


Effects of ultraviolet-A exposure on ultraviolet-B-induced accumulation of specific flavonoids in Brassica napus.
Many plant species are able to acclimate to changes in ultraviolet-B radiation (UVB) (290-320 nm) exposure. Due to the wide range of targets of UVB, plants have evolved diverse repair and protection mechanisms. These include increased biosynthesis of UVB screening compounds, elevated antioxidant activity and increased rates of DNA repair. We have shown previously that Brassica napus L. cv Topas plants can acclimate quite effectively to environmentally relevant increases in UVB through the accumulation of specific flavonoids in the leaf epidermis. However, B. napus was found to lose other flavonoids when plants are exposed to ultraviolet-A radiation (UVA) (320-400 nm) and/or UVB (Wilson et al. [1998] Photochem. Photobiol. 67, 547-553). In this study we demonstrate that the levels of all the extractable flavonoids in the leaves of B. napus plants are decreased in a dose-dependent manner in response to UVA exposure. Additionally, the accumulation of the extractable flavonoids was examined following a shift from photosynthetically active radiation (PAR) + UVA to PAR + UVB to assess if preexposure to UVA affected UVB-induced flavonoid accumulation. UVA preexposures were found to impede UVB-induced accumulation of some flavonoids. This down regulation was particularly evident for quercetin-3-O-sophoroside and quercetin-3-O-sophoroside-7-O-glucoside, which is interesting because quercetins have been demonstrated to be induced by UVB and correlated with UVB tolerance in some plant species. The photobiological nature of these UVA-mediated effects on flavonoid accumulation implies complex interactions between UVA and UVB responses.


Introduction to ISO 15189: a blueprint for quality systems in veterinary laboratories.
A trend in human and veterinary medical laboratory management is to achieve accreditation based on international standards. The International Organization for Standardization (ISO) 15189 standard is the first developed especially for accreditation of medical laboratories, and emphasizes the laboratory-client interface. European veterinary laboratories seeking to train candidates for the certification examination of the European College of Veterinary Clinical Pathology (ECVCP) require approval by the ECVCP Laboratory Standards Committee, which bases its evaluation in part on adherence to quality systems described in the ISO 15189 standards. The purpose of this article was to introduce the latest ISO quality standard and describe its application to veterinary laboratories in Europe, specifically as pertains to accreditation of laboratories involved in training veterinary clinical pathologists. Between 2003 and 2006, the Laboratory Standards Committee reviewed 12 applications from laboratories (3 commercial and 9 university) involved in training veterinary clinical pathologists. Applicants were asked to provide a description of the facilities for training and testing, current methodology and technology, health and safety policy, quality assurance policy (including internal quality control and participation in an external quality assurance program), written standard operating procedures (SOPs) and policies, a description of the laboratory information system, and personnel and training. Also during this time period multiple informal and formal discussions among ECVCP diplomates took place as to current practices and perceived areas of concern with regard to laboratory accreditation requirements. Areas in which improvement most often was needed in veterinary laboratories applying for ECVCP accreditation were the written quality plan, defined quality requirements for the tests performed, written SOPs and policies, training records, ongoing audits and competency assessments, and processes for identifying and addressing opportunities for improvement. Recommendations were developed for a stepwise approach towards achieving ISO 15189 standards, including 3 levels of quality components. The ISO 15189 standard provides a sound framework for veterinary laboratories aspiring to meet international quality standards.


Spectral Characterization of Three-Electron Two-Center (3e-2c) Bonds of Gaseous CH3S∴S(H)CH3 and (CH3SH)2+ and Enhancement of the 3e-2c Bond upon Protonation.
The three-electron two-center (3e-2c) bond plays an important role in structures and electron communication in biological systems involving cationic sulfur compounds. Although the nature of 3e-2c bonds and their theoretical formalism have attracted great interest, direct spectral identifications of 3e-2c-bound molecules are scarce. We observed the infrared spectra of the weakly 3e-2c-bound CH3S∴S(H)CH3 and the strongly 3e-2c-bound (CH3SH)2+ in a supersonic jet using infrared (IR) dissociation with vacuum-ultraviolet photoionization and time-of-flight detection. Protonation of CH3S∴S(H)CH3 to form [CH3(H)S∴S(H)CH3]+ significantly enhances the 3e-2c bond, characterized by a large red shift of the SH-stretching band with enhanced IR intensity, shortening of the calculated S-S distance from 3.00 to 2.86 Å, and a dissociation energy increased from ∼23 to 162 kJ mol-1.


Surface roughness and material removal in fluid jet polishing.
Based on experiments, the dependence of material removal and surface roughness on the characteristics of abrasive particles, on the workpiece, and on other process parameters such as working pressure and incidence angle in fluid jet polishing (FJP) technology were investigated. Experimental results show a volume removal rate that is approximately proportional to the square root of the Young's modulus (E) and inversely proportional to the square of the Knoop hardness (Hk) of glass. Similarly, surface roughness is also determined in FJP by elastic stiffness E and plastic parameter Hk. The influence of the incidence angle on surface roughness and material removal were studied, and a linear dependence of material removal on the working pressure was obtained. Further, it was found that an optical-quality surface can be achieved by use of Cerox 1650 abrasive particles in FJP and can satisfy the requirements of modern optical manufacturing.


Inhibitory action of propranolol on the contractions induced by nerve stimulations or calcium in the smooth muscle of rat vas deferens.
Inhibitory effects of propranolol on the contractions to various treatments were investigated in the epididymal half of the rat vas deferens. Reportedly, 10(-5)-3 X 10(-4) M propranolol inhibited 150 mM K-induced contractions dose-dependently; 3 X 10(-4) M propranolol abolished the contractions. The present results showed that propranolol at concentrations up to 10(-4) M did not inhibit the maximal contractions to 10(-3) M norepinephrine (NE) or 10(-2) M methacholine (MCh). Propranolol at 3 X 10(-4) M slightly inhibited contractions to NE and MCh by 11% and 12%, respectively. In contrast, propranolol inhibited twitch components of the contractions induced by nerve stimulations at similar doses to those reported for high K contractions. Propranolol also inhibited contractions to Ca in high K-containing solution and shifted the dose-response curve to the right. Propranolol did not affect the depolarizations by high K measured by microelectrodes. Propranolol at concentrations of 10(-5)-3 X 10(-5) M diminished the magnitude of spikes dose-dependently. Spikes were rarely observed in the presence of 10(-4) M propranolol in spite of generation of e.j.p.s with amplitudes that would be sufficient to induce spikes in the absence of propranolol. These results suggest that propranolol inhibits contractions by decreasing Ca-influx through the potential-operated Ca-channels in the smooth muscle cells of rat vas deferens.


Helix formation in arrestin accompanies recognition of photoactivated rhodopsin.
Binding of arrestin to photoactivated phosphorylated rhodopsin terminates the amplification of visual signals in photoreceptor cells. Currently, there is no crystal structure of a rhodopsin-arrestin complex available, although structures of unbound rhodopsin and arrestin have been determined. High-affinity receptor binding is dependent on distinct arrestin sites responsible for recognition of rhodopsin activation and phosphorylation. The loop connecting beta-strands V and VI in rod arrestin has been implicated in the recognition of active rhodopsin. We report the structure of receptor-bound arrestin peptide Arr(67-77) mimicking this loop based on solution NMR data. The peptide binds photoactivated rhodopsin in the unphosphorylated and phosphorylated form with similar affinities and stabilizes the metarhodopsin II photointermediate. A largely alpha-helical conformation of the receptor-bound peptide is observed.


Use of Differential Entropy for Automated Emotion Recognition in a Virtual Reality Environment with EEG Signals.
Emotion recognition is one of the most important issues in human-computer interaction (HCI), neuroscience, and psychology fields. It is generally accepted that emotion recognition with neural data such as electroencephalography (EEG) signals, functional magnetic resonance imaging (fMRI), and near-infrared spectroscopy (NIRS) is better than other emotion detection methods such as speech, mimics, body language, facial expressions, etc., in terms of reliability and accuracy. In particular, EEG signals are bioelectrical signals that are frequently used because of the many advantages they offer in the field of emotion recognition. This study proposes an improved approach for EEG-based emotion recognition on a publicly available newly published dataset, VREED. Differential entropy (DE) features were extracted from four wavebands (theta 4-8 Hz, alpha 8-13 Hz, beta 13-30 Hz, and gamma 30-49 Hz) to classify two emotional states (positive/negative). Five classifiers, namely Support Vector Machine (SVM), k-Nearest Neighbor (kNN), Naïve Bayesian (NB), Decision Tree (DT), and Logistic Regression (LR) were employed with DE features for the automated classification of two emotional states. In this work, we obtained the best average accuracy of 76.22% ± 2.06 with the SVM classifier in the classification of two states. Moreover, we observed from the results that the highest average accuracy score was produced with the gamma band, as previously reported in studies in EEG-based emotion recognition.


Acute action of DSP-4 on central norepinephrine axons: biochemical and immunohistochemical evidence for differential effects.
Previous immunohistochemical studies of the long-term effects of the noradrenergic neurotoxin DSP-4 have demonstrated a remarkably selective vulnerability of norepinephrine (NE) axons of the locus coeruleus (LC). NE axons originating in non-LC NE neurons appear to be largely resistant to the neurotoxic action of DSP-4. We conducted this study to evaluate the acute effects of DSP-4 on NE axons in four different brain regions: cerebral cortex, cerebellum, ventral forebrain, and hypothalamus. NE levels were determined by high-performance liquid chromatography (HPLC) 6 and 24 hr and 14 days after DSP-4 administration. NE axons in these brain regions were visualized in brain sections at 6 and 24 hr after drug treatment, using a specific antiserum to NE. HPLC assays revealed profound reductions of NE levels in cerebral cortex and cerebellum, but only minor decreases in ventral forebrain and hypothalamus. NE immunohistochemistry showed dramatic differences in the acute effects of DSP-4 on NE axon staining: nearly complete loss of staining in cortex and cerebellum, in contrast to an almost unchanged staining pattern in ventral forebrain and hypothalamus. This study demonstrates that NE immunohistochemistry is a valuable tool to assess the acute effects of DSP-4 on NE axons in different brain regions. The results provide the first direct evidence that NE axons are not uniformly acted on by DSP-4 and suggest that the acute effects of DSP-4 are restricted to LC axons.


Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity.
The increasing number of recording electrodes enhances the capability of capturing the network's cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.


Cancer mortality among female and male workers occupationally exposed to inorganic lead in the printing industry.
Evaluation of the carcinogenicity of lead for humans has been based primarily on the results of studies on occupationally exposed men, although gender differences in lead metabolism have been reported. In addition, most of the previous studies have been limited by a failure to identify and control for co-exposures to other known occupational carcinogens. The present study follows an industrial cohort of workers, mostly women, with moderate lead exposure and no confounding by other occupational exposures. Workers, employed at least 2 years between 1950 and 1978 in manual and mechanical (linotype) typesetting and type foundries in 27 printing plants in Moscow, were included in the cohort, which comprised 1423 men and 3102 women. The cohort was followed up during 1979-2003 and contributed 93,682 person-years of observation. Follow-up was 97.7% complete. Standardised mortality ratios (SMRs) and 95% CIs, based on mortality rates of the Moscow general population and adjusted for gender, age and calendar time, were calculated for the total cohort as well as subcohorts stratified by various exposure parameters. Among women, mortality from all causes, circulatory diseases and all cancers combined was lower than that in the Moscow general population and was similar across work groups. Among men, there was excess overall mortality, mainly due to increased mortality from ischaemic heart disease. For both sexes, no significant excess risk for any cancer site was observed, although some dose-response patterns were found. In the overall cohort, mortality from cancers of the kidney and pancreas increased up to twofold in the highest tertile of cumulative lead exposure based on duration and a relative ranking of the three subcohorts (9 deaths; SMR=2.12, 95% CI 1.10 to 4.07) and (18 deaths; SMR=2.32, 95% CI 1.46 to 3.68), respectively. Similar mortality trends for these two cancers were found in analyses by gender. Consistencies by sex and exposure level make a strong case for a link between exposure to inorganic lead and cancers of the kidney and pancreas.


[Use of simethicone in the prevention of postoperative abdominal discomfort and gastrointestinal distension after cesarean section].
A double blind trial was performed in patients with Cesarean section in order to study the effect of Simeticon (Stuart Pharmaceutical Company, Pasadena, California) on the occurrence of subjective and objective signs of gas distress during the immediate postoperative period. The results obtained with Simeticon show a highly significant reduction of the analysed subjective complaints (nausea, vomiting, meteorism, discomfort in the stomach, abdominal pains) in relation to placebo. Peristaltic movements in patients treated with Simeticon appeared in the first two days in 100% of cases and only in 30% in the placebo group. Flatulence also appeared in all the patients receiving Simeticon, in contrast to only 20% in the placebo group. There was no difference in spontanous defecation between the groups. On the basis of the results obtained, and considering the non-toxicity of the drug, its chemical inertnees, good tolerance, and simple use, the authors consider simeticon very useful for the prevention and therapy of postoperative discomfort due to gas accumulation and gastro-intestinal distention after Cesarean section.


Relative number of long- and middle-wavelength-sensitive cones in the human fovea.
Flicker photometric measurements yield spectral sensitivity curves that are well fitted by sums of the spectral sensitivity curves of long-wavelength-sensitive (L) cones and middle-wavelength-sensitive (M) cones if the L cones are given twice the weight of the M cones. This result has been interpreted as implying that L cones are more numerous than M cones but is also consistent with a different numerical ratio, say, 1:1, and with the assignment of greater weight to the L cone input than to the M cone input by the mechanism subserving flicker photometry. Measurements of temporal sensitivity are presented for lights that modulate the inputs of either only the L cones or only the M cones. Sensitivity to modulation of the L cones is approximately twice that of modulation of the M cones at approximately 30 Hz, but that advantage disappears at approximately 2 Hz. Thus flicker sensitivity is equivocal with regard to cone numerosity. Electrophysiological, anatomical, and psychophysical evidence is reviewed, with particular weight placed on the statistics of color appearance of small, brief, monochromatic lights and on increment thresholds measured on the same observers. It is concluded that, in the central fovea, the ratio of L:M cone numbers is close to unity and may not be so variable as is usually supposed.


Nutrition and cognition: meeting the challenge to obtain credible and evidence-based facts.
Nutrition provides a practical and appealing approach to cognitive enhancement, including the modulation of long-term cognitive processes such as neurodevelopment and neurodegeneration. An abundance of promising nutritional influences on cognition have been identified, but many long-term effects remain to be confirmed by data from randomized controlled trials (RCTs). The current article provides a general outline of various factors that hamper the demonstration of causal long-term nutritional effects on cognition by RCTs and advocates the development of methodological solutions to enable substantiation in future RCTs.


[The prevalence of hepatitis A in the Guadalajara province. Is Spain a country with low endemia?].
Spain, together with the other southern European countries, was considered to be an area with a moderate degree of endemia. This fact has consequences for tourists that visit these areas and for vaccination strategies. A prevalence study was proposed in order to get to know the situation of this infection in the Guadalajara province. 284 specimens of serum were taken from patients who were classified according to their age, sex and place of residence (with more or less than 10.000 inhabitants). In these specimens the presence of hepatitis A antibodies were studied, using a Microparticule Enzyme Immunoassay (MEIA) (Abbott). An increase in the prevalence was observed in older people, there is a low prevalence population (</= 5%) in people aged between 0-29 years and a high prevalence population (>80%) in adults aged between 30 and 74 years. No differences were observed related to sex. In the stratified analysis according to age, differences were observed between the groups from rural and urban origins. The low prevalence of hepatitis A was found among the younger population, as seen in other studies carried out on a national level, and this together with a decrease in the frequency, means that Spain is included among the countries with low endemia. This fact has consequences for tourists who visit our country and for vaccination strategies, due to the increase in the number of adults who are susceptible to the infection.


Serial changes of tricuspid regurgitation after anatomic repair for congenitally corrected transposition.
The aim of this study was to reveal the serial changes in tricuspid regurgitation (TR) after anatomic repair for congenitally corrected transposition of great arteries. Between 1995 and 2018, 48 patients underwent anatomic repair (atrial/arterial switch in 14 patients, atrial switch and Rastelli in 34 patients). The mean age and weight of the patients during anatomic repair was 33 (interquartile range 21.8-62.1) months and 12 (10.3-16.3) kg. The preoperative TR was less than mild in 15 patients (31.3%), mild-to-moderate in 29 patients (60.4%) and more-than-moderate in 4 patients (8.3%). Ebsteinoid dysplasia of the tricuspid valve (TV) was observed in 7 patients (14.6%). During the study period, no patient underwent TV surgery or bidirectional Glenn anastomosis at the time of anatomic repair. There was 1 in-hospital death and 1 late death. The follow-up was completed by other surviving patients, with a median follow-up period of 12.1 years (5.9-18.1). The overall survival, reoperation-free survival and freedom from permanent pacemaker implantation rate at 15 years were 94.3%, 74.3% and 81.5%, respectively. The mean TR grade was 2.0 (1.0-2.6) preoperatively, 2.0 (1.0-2.0) at 1 year, 2.0 (2.0-2.0) at 5 years and 2.0 (2.0-2.0) at 10 years after anatomic repair. A Cox proportional hazards model showed that association of Ebsteinoid dysplasia of the TV, type of anatomic repair and previous pulmonary artery banding did not affect freedom from death or the more-than-moderate TR rate. There were 2 patients who underwent TV surgery after the anatomic repair for severe TR; TV repair was successfully done for 1 patient, the other required semi-closure of TV and one and one-half ventricle conversion. TR remained subclinical or improved in the majority of patients after anatomic repair without TV repair. However, there were a few patients whose TR progressed to severe or massive, then required TV surgery after anatomic repair. Although exposure was difficult, TR was sometimes repairable following atrial switch, otherwise, one and one-half ventricle repair conversion would be the choice of treatment.