Inhibition of growth of estrogen receptor positive and estrogen receptor negative breast cancer cells in culture by AA-etherA, a stable 2-5A derivative.
The design, chemical synthesis and biological activities of a nuclease-resistant, nontoxic bioactive 2-5A derivative, AA-etherA [i.e., adenylyl-(2'-5')-adenylyl-(2'-2")-9-[(2'-hydroxyethoxy)-methyl]adenine], are described as a new approach to the inhibition of breast cancer cell growth. AA-etherA inhibits DNA replication and cell division of both estrogen receptor positive (MCF-7) and estrogen receptor negative (BT-20) breast cancer cells in culture in a dose-dependent manner. Maximal inhibition in MCF-7 and BT-20 cells was obtained with 100 microM AA-etherA after four days of treatment, with an GI50 of 58 and 37 microM, respectively. AA-etherA is stable in the cytoplasm. Treated cells accumulate within the late G1/early S phase of the cell cycle and then progress only very slowly through S phase. AA-etherA does not activate RNase L, as do 2-5A and other 2-5A derivatives, nor does it increase p68 kinase (PKR) content of the cells. High resolution, two-dimensional protein gel electrophoresis reveals twofold or greater inhibition of synthesis of 92 proteins out of 682 proteins that were reproducibly detected as high quality spots with average rates of synthesis of > or = 20 p.p.m. in untreated cells. The specificity of the effects of AA-etherA on select proteins and its failure to activate RNase L indicate that AA-etherA does not act through a general effect on mRNA translation or stability, but rather inhibits cell proliferation through a block to DNA replication, with a concommitant reduction in the synthesis of specific proteins, some of which may be required for cell cycle transit. Two likely targets to account for the AA-etherA inhibition of DNA replication are DNA topoisomerase I, which is inhibited by AA-etherA in other cell lines, and thymidine kinase, which could be inhibited in a manner similar to the effect of acyclovir. These data indicate that 2-5A analogs, particularly bifunctional 2-5A analogs like AA-etherA, will be useful for controlling cancer cell growth. Further development of such 2-5A analogs may provide highly specific compounds for chemotherapy and chemoprevention.


[Pleural fibroma. Contribution of immunohistochemistry].
The authors report a case of pleural fibroma discovered during an examination for thoracic pains in a 65 year old woman. Histochemical studies were positive with vimentin and negative with KL1 antibodies and compatible with the most recent hypotheses concerning the purely fibroblastic origin of these tumours.


[Development of fluorinated pyrimidines in Japan].
Four fluorinated pyrimidines that are in the stage of clinical trials at present in Japan were reviewed: BOF-A2, Ro09-1390, TT-62 and S-1. Both BOF-A 2 and S-1 are a compound of 5-FU derivative combined or mixed with an inhibitor of 5-FU degradation in order to prolong the blood 5-FU level as well as increase selective toxicity to tumor. Furthermore, an inhibitor of 5-FU phosphorylation in G1 tract contained in S-1 reduces G1 toxicity such as diarrhea etc due to prolongation of blood 5-FU level. Ro09-1390 is an improved compound of 5'-DFUR, which intends to reduce diarrhea caused by the latter. TT-62 is a FdUMP derivative and an active metabolite of 5-FU for oral formulation, which is superior to available 5-FU type anticancer agents in efficacy, and doesn't show cross tolerance to 5-FU.


A New Potential Strategy for Acute Non-Alcoholic Steatohepatitis (NASH).
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States, and 25% of patients with NAFLD progress to non-alcoholic steatohepatitis (NASH). NAFLD is predicted to be the most common indication for liver transplantation by 2030. Despite associated high morbidity and mortality, there is currently no approved therapy for NASH. PCSK9 inhibitors are approved for reducing LDL in patients who are statin-intolerant or need further LDL reduction. Increased LDL levels are independently associated with an elevated risk of NAFLD. CASE REPORT We present a case of a 39-year-old woman with acute NASH with familial hypercholesterolemia that was refractory to lifestyle modifications and HMG-CoA reductase inhibitors. An episode of rhabdomyolysis warranted a search for alternatives to statin therapy. Results of a liver biopsy showed microvesicular and macrovesicular steatosis with ballooning degeneration, indicating acute NASH. She was started on PCSK9 inhibitors as salvage therapy. Three monthly doses resulted in a more than an 80% reduction in ALT and AST and a 48% reduction in LDL levels. A liver biopsy done 8 months after the first biopsy showed normalization of liver histology. CONCLUSIONS The use of PCSK9 inhibitors showed a dramatic response in this patient who failed conventional therapies, and the encouraging results seen in this case merit further research into the use of PCSK9 inhibitors as first-line therapy for the acute phase of NASH.


Endoscopic ultrasound-guided management of pancreatic pseudocysts and walled-off necrosis.
The outcome of endoscopic management of pancreatic fluid collections is dependent on the type of collection being treated. While pseudocysts have an excellent treatment response, the outcomes are modest for walled-off pancreatic necrosis. Recent advances in cross-sectional body imaging have enabled a more accurate distinction of pancreatic fluid collections, which, in turn, facilitates the correct triage of patients to receive the appropriate treatment. Newly described endoscopic techniques and the development of dedicated accessories have improved the clinical outcomes in walled-off pancreatic necrosis, with treatment success rates comparable to that of minimally invasive surgery. This review summarizes the key concepts and provides a concise update on the endoscopic management of pancreatic fluid collections.


The role of endoplasmic reticulum-associated protein degradation in MHC class I antigen processing.
The processing and presentation of secretory glycoprotein antigens by the MHC class I processing pathway presents an interesting topological problem. That is, how do the luminal glycoprotein antigens gain access to the class I processing machinery located in the cell cytosol? Current data indicate that the retrograde transport of glycoproteins from the endoplasmic reticulum (ER) to cytosol represents the major pathway for ER-associated protein degradation, and most likely represents a major pathway for the processing of glycoprotein antigens by MHC class I molecules as well. There is now a growing list of viral and tumor glycoprotein antigens that undergo retrograde transport from the ER to the cytosol and processing by the ubiquitin-proteasome pathway of degradation. We review here some general aspects of this "ER degradation" pathway, and how it relates to the processing and presentation of class I-associated viral and tumor antigens. In particular, we analyze the role of oligosaccharide trimming and ER molecular chaperones in this process. We would like to emphasize that the class I processing machinery has adapted a common cellular pathway for its use, and that this could lead to the identification of unique characteristics with regard to ER degradation and antigen processing.


The ACT-4D: a novel rehabilitation robot for the quantification of upper limb motor impairments following brain injury.
Rehabilitation robots and other controlled diagnostic devices are useful tools to objectively quantify debilitating, post-stroke impairments. The goal of this paper is to describe the design of the ACT-4D rehabilitation robot which can quantify arm impairments during functional movement. The robot can instantly switch between a compliant mode that minimizes impedance of voluntary movement, and a stiff mode that applies controlled position/speed perturbations to the elbow (up to 75 Nm or 450 deg/s at 4500 deg/s(2)). It has a limited range of movement of the shoulder and elbow, which is further reduced when a damper is needed to enhance the positional stiffness of the base robot. In recent experiments, the ACT-4D has been used successfully for the quantification of elbow impairments.


The efficacy of triplet antiemetic therapy with 0.75 mg of palonosetron for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy.
Chemotherapy-induced nausea and vomiting (CINV) are some of the most problematic symptoms for cancer patients. Triplet therapy consisting of a 5HT3 receptor antagonist, aprepitant, and dexamethasone is a guideline-recommended antiemetic prophylaxis for highly emetogenic chemotherapy (HEC). The efficacy and safety of triplet therapy using a 0.75-mg dose of palonosetron have not yet been investigated. We performed a prospective phase II study using triplet antiemetic therapy with 0.75 mg of palonosetron. Chemotherapy-naïve lung cancer patients scheduled to receive HEC were enrolled. The eligible patients were pretreated with antiemetic therapy consisting of the intravenous administration of 0.75 mg of palonosetron, and 9.9 mg of dexamethasone and the oral administration of 125 mg of aprepitant on day 1, followed by the oral administration of 80 mg of aprepitant on days 2-3 and the oral administration of 8 mg of dexamethasone on days 2-4. The primary endpoint was the complete response rate (the CR rate; no vomiting and no rescue medication) during the overall phase (0-120 h). The efficacy analysis was performed in 63 patients. The CR rates during the overall, acute and delayed phases were 81.0, 96.8, and 81.0%, respectively. The no nausea and no significant nausea rate during the overall phase were 54.0 and 66.7%, respectively. The most common adverse event was grade 1 or 2 constipation. Triplet antiemetic therapy using a 0.75-mg dose of palonosetron shows a promising antiemetic effect in preventing CINV in lung cancer patients receiving HEC.


Liquid nitrogen therapy.
Benign skin lesions such as solar and seborrhoeic keratoses, viral warts, and skin tags can be treated successfully by cutaneous cryotherapy. Complications are infrequent if the correct technique is used and local anaesthetic usually is unnecessary. Liquid nitrogen (boiling point -196 degrees C) is the usual freezing agent but carbon dioxide snow (-79 degrees C) is an adequate substitute.


Kinetics of the solvolyses of benzhydryl derivatives: basis for the construction of a comprehensive nucleofugality scale.
A series of 21 benzhydrylium ions (diarylmethylium ions) are proposed as reference electrofuges for the development of a general nucleofugality scale, where nucleofugality refers to a combination of leaving group and solvent. A total of 167 solvolysis rate constants of benzhydrylium tosylates, bromides, chlorides, trifluoroacetates, 3,5-dinitrobenzoates, and 4-nitrobenzoates, two-thirds of which have been determined during this work, were subjected to a least-squares fit according to the correlation equation log k(25 degrees C) = sf(Nf + Ef), where sf and Nf are nucleofuge-specific parameters and Ef is an electrofuge-specific parameter. Although nucleofuges and electrofuges characterized in this way cover more than 12 orders of magnitude, a single set of the parameters, namely sf, Nf, and Ef, is sufficient to calculate the solvolysis rate constants at 25 degrees C with an accuracy of +/-16 %. Because sf approximately 1 for all nucleofuges, that is, leaving group/solvent combinations, studied so far, qualitative discussions of nucleofugality can be based on Nf.


Motion correction in exercise first-pass radionuclide ventriculography without an external point source.
Exercise first-pass radionuclide ventriculography provides valuable diagnostic and prognostic information in patients with coronary artery disease. In this procedure, motion correction of the images is commonly performed using a second external point source attached to the chest wall during exercise (dual-isotope method). Recently, a motion correction algorithm without an external point source (single-isotope method) was developed and the results compared with those of the dual-isotope method. To examine the accuracy of the motion correction method, a phantom study was performed using a moving cardiac phantom with a motion speed of up to 169 cycle/min and motion amplitude up to 6 cm. Count fluctuation in the phantom region by motion was calculated as a coefficient of variation (CV). In the clinical study, time-activity curves of the left ventricular phase were created for quantitative assessment of variation as CV values of the ejection fraction in the central five cardiac cycles after correction by the two methods during exercise radionuclide ventriculography in 17 patients. In the moving phantom, both the single- and dual-isotope methods reduced the CV values less than 10%. In the clinical study, the single-isotope method provided less CV value of ejection fraction (9.8% +/- 5.6%) than the dual-isotope method (24.8% +/- 10.5%) (p < 0.01), indicating less individual variation of ejection fraction values. These data indicate that object motion can be accurately corrected in the moving phantom by both single- and dual-isotope methods. In clinical studies, the single-isotope method is more accurate.


Midlife Factors Related to Psychological Well-Being at an Older Age: Study of Women's Health Across the Nation.
Background: Psychological well-being (PWB) is predictive of future health and mortality. Midlife is a pivotal time in women's lives and may impact future PWB. This study, based on a longitudinal cohort of women, sought to identify how personal and social resources and modifiable behaviors at midlife relate to women's PWB in later life, and to determine if psychological resilience in later life moderates the impact of health problems on PWB. Materials and Methods: We assessed the association of midlife factors with PWB ∼9 years later in 1693 women from the multiracial/ethnic Study of Women's Health Across the Nation (SWAN) cohort. PWB was a composite score with cognitive and affective components. Midlife factors included sociodemographics, health, menopause-related, and psychosocial factors collected over the course of midlife. Results: In a multivariable model, greater PWB at an older age was associated with the following at midlife: less financial strain, greater physical activity, not smoking, better physical functioning, and fewer sleep problems. More positive attitudes toward menopause and aging, less cynicism, greater optimism, less trait anxiety, greater spirituality, and greater resilience were also independently associated with better PWB. Chinese women reported lower PWB compared with whites. Later life resilience moderated the impact of sleep problems on PWB. Conclusions: Several modifiable factors at midlife are associated with better PWB in older women and highlight the importance of healthy behaviors such as physical activity and good sleep hygiene at midlife. Interventions to increase optimism, spirituality, and resilience are also worth exploring.


Possible mechanism of induction of benign prostatic hyperplasia by estradiol and dihydrotestosterone in dogs.
A mechanism of induction of canine benign prostatic hyperplasia (BPH) by androgen-stimulated growth of prostatic cells exposed to estrogen-induced toxicity. Estrogen is thought to be activated by redox cycling of catechol metabolites, a mechanism of generation of active radicals. Mongrel dogs, 4 animals/group, were sham-operated (controls) or were treated for 60 days with implants of 5 alpha-dihydrotestosterone and/or estradiol-17 beta. The activities of drug and hormone metabolizing enzymes (aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase, and estradiol-17 beta-2- and -4-hydroxylase) in prostate were significantly elevated by chronic treatment with either estradiol-17 beta or 5 alpha-dihydrotestosterone plus estradiol-17 beta, but not in kidney or liver which are not targets of hormone-induced hyperplasia. Activities of the detoxifying enzymes catalase and glutathione peroxidase I in prostate were increased by estradiol-17 beta treatment, whereas in kidney or liver they were not affected or changed to a lesser degree than observed in prostate. Free radial-induced damage (carbonyl content) of proteins was observed in prostate of dogs treated with either estradiol-17 beta or 5 alpha-dihydrotestosterone plus estradiol-17 beta and in liver protein by treatment with either 5 alpha-dihydrotestosterone or 5 alpha-dihydrotestosterone plus estradiol-17 beta. It was concluded that the patterns of estradiol-17 beta- or 5 alpha-dihydrotestosterone plus estradiol-17 beta-induced increases in activities of catechol estrogen synthase and of other drug metabolizing enzymes were consistent with the postulated free radical generation by redox cycling of catechol estrogen specifically in the prostate. The increases in activities of detoxifying enzymes may represent an (albeit insufficient) response to prostatic free radical damage to protein in prostate is consistent with a postulated induction of BPH via injury by estrogen metabolites followed by 5 alpha-dihydrotestosterone-stimulated growth of altered prostatic cells.


Bradykinin B1 receptor up-regulation by interleukin-1beta and B1 agonist occurs through independent and synergistic intracellular signaling mechanisms in human lung fibroblasts.
Bradykinin B1 receptors (B1R) are rapidly induced after tissue trauma and are thought to be involved in maintaining the inflammatory response. Little is known about the intracellular signaling pathways mediating B1R induction in response to stress and inflammation. Here, we show that up-regulation of B1R by B1R agonist and interleukin-1beta (IL-1beta) occur through distinct but synergistic pathways in IMR-90 human lung fibroblasts. Incubation of cells with the B1R agonist desArg10kallidin (desArg10KD; 100 nM) and IL-1beta (500 pg/ml) resulted in a 3- and 4-fold increase, respectively, in B1R by 6 h, whereas coincubation of these factors produced up to a 20-fold increase. Furthermore, coincubation increased the potency of IL-1beta by 2-fold. Both the individual and the synergistic responses were sensitive to genistein, a general tyrosine kinase inhibitor. On the other hand, only the desArg10KD response and the synergistic response were sensitive to the p38 mitogen-activated protein kinase inhibitor SB 203580. Furthermore, only the synergistic response was sensitive to the nuclear factor-kappaB inhibitor pyrrolidine dithiocarbamate. Despite B1R up-regulation in A549 human lung epithelial cells by desArg10KD or IL-1beta individually, these factors did not act synergistically in this cell line. In conclusion, our results reinforce the view that kinins act in concert with proinflammatory cytokines to enhance selectively the inflammatory response of certain lung cells to kinins through distinct but synergistic intracellular signaling mechanisms. Thus, kinins may exert a pivotal role in maintaining and modulating feed-forward inflammatory processes in the lung.


[Comparison of congenital color vision deficiencies prevalence between Han and Uygur high-school students].
A population-based study was conducted to compare the prevalence of congenital color vision deficiencies (CVD) in high-school students of Uygur and Han nationalities in Xinjiang Uygur autonomous region. Students from 7 high schools were examined with pseudoisochromatic color plates and further with Farnsworth Munsell 100 test. The chi-square test was applied to compare categorical variables, and the independent-samples t test was used to compare the measure data. In the study population of 3764 Uygur students, 88 students had CVD, including 69 males and 19 females. 48 of 2055 Han students were diagnosed with CVD, including 46 males and 2 females. No significant difference existed in the prevalence of CVD in boys between two nationalities. The prevalence of CVD in Uygur girls was higher than that in Han girls. No significant difference was found in the prevalence of CVD in boys between two nationalities. The prevalence of CVD in Uygur girls was higher than that in Han girls.


Neurochemical studies of an analgesic, 1,3-diphenyl-5-(2-dimethylaminopropionamide)-pyrazole [difenamizole].
For the purpose of clarifying the action mechanism of the analgesic agent, difenamizole (DFZ), chemically known as 1,3-diphenyl-5-(2-dimethylaminopropionamide)-pyrazole, the following properties were investigated: 1) monoamine metabolizing enzymes, 2) biosynthesis of dopamine (DA), 3) binding of DA on the synaptic membrane of mice, 4) uptake of catecholamine (CA) by synaptosome in discrete brain areas and 5) DA release from the striatal slices of mice. Pertinent results obtained are delineated below: 1) DFZ at 10(-4) M inhibited the monoamine oxidase (MAO) activity to some extent although it had no activity on catechol-O-methyltransferase (COMT) at 10(-6) -10(-4) M. 2) DFZ significantly enhanced the DA accumulating activity of pargyline in the striatum. 3) DFZ inhibited the binding of 3H-DA to synaptic membrane by 25% at 10(-4) M in the striatum. 4) DFZ inhibited the DA uptake by 50% at 10(-4) M though the activity was somewhat weaker than imipramine or cocaine on the striatum. 5) DFZ inhibited the DA release due to high K+ concentration in striatal slices at 10(-4) -5x10(-4) M. From the above data, it was concluded that DFZ may exert its analgesic effect by inhibiting the release of DA and preventing the binding of DA with the receptors.


[A teaching experience of Evidence Based Prevention].
One year after a 3-day training course on EBP (Evidence Based Prevention), the 130 participants were sent a follow-up questionnaire intended to estimate the persistence of knowledge and the extent of the use of evaluation techniques in EBP. Although respondents to the questionnaire (73%) and participants to the course were not representative of workers in the health field area, results clearly indicate that major drawbacks the use of EBP are the organization of daily work in prevention activities and the limited knowledge of English (i.e. the language in which most scientific literature related to EBP is available). More education on EBP is advisable, including the application of distant learning techniques into the frame of Continuous Medical Education for all Italian professionals involved in Prevention.


Violence against women migrant workers: issues, data and partial solutions.
"Despite the creation of specific norms, procedures, and institutions to protect women migrant workers, serious gaps remain. Statistics for measuring violence are not compiled comprehensively or regularly. Two occupations that increase the risk of violence are domestic service and entertainment-related services. Migration through illegal channels and trafficking also increase the risk. This article suggests a list of indicators to measure violence of three major types: (1) economic, (2) social/psychological, and (3) physical/sexual. Evidence from several countries to document instances of violence is reviewed. Major policy issues for the sending and receiving countries are outlined, and some recommendations for addressing such violations are made."


Lensless zoomable holographic projection using scaled Fresnel diffraction.
Projectors require a zoom function. This function is generally realized using a zoom lens module composed of many lenses and mechanical parts; however, using a zoom lens module increases the system size and cost, and requires manual operation of the module. Holographic projection is an attractive technique because it inherently requires no lenses, reconstructs images with high contrast and reconstructs color images with one spatial light modulator. In this paper, we demonstrate a lensless zoomable holographic projection. Without using a zoom lens module, this holographic projection realizes the zoom function using a numerical method, called scaled Fresnel diffraction which can calculate diffraction at different sampling rates on a projected image and hologram.


Non-invasive stroke volume estimation by transthoracic electrical bioimpedance versus Doppler echocardiography in healthy volunteers.
Thoracic electrical bioimpedance (TEB) and transthoracic echocardiography (TTE) are non-invasive methods to estimate stroke volume (SV) and cardiac output (CO). Thoracic electrical bioimpedance is not in widespread clinical use with reports of inaccurate cardiac output estimation compared to invasive monitors, particularly in non-healthy populations. We explore its use as a trend monitor by comparing it against thoracic echocardiography in fifteen healthy volunteers undergoing two physical challenges designed to vary cardiac output. Of all paired values, 54.6% showed gross trend agreement and only 1.9% showed direct disagreement between the two monitors. Our results show thoracic bioimpedance may have a role as a non-invasive cardiac output trend monitor in healthy volunteer studies.


In vivo evidence that the lipid-regulating activity of the ACAT inhibitor CI-976 in rats is due to inhibition of both intestinal and liver ACAT.
CI-976, a new trimethoxy fatty acid anilide, is a potent and specific inhibitor of liver and intestinal acyl coenzyme A:cholesterol acyltransferase (ACAT) in vitro. Several in vivo approaches were used to determine the efficacy and sites of action of this compound in rats. CI-976 decreased non-high density lipoprotein (HDL)-cholesterol and increased HDL-cholesterol in rats with pre-established dyslipidemia. High performance gel chromatographic separation of plasma lipoproteins also revealed that CI-976, but not CL 277,082, lowered low density lipoprotein (LDL)-cholesterol and elevated HDL-cholesterol. Bay o 2752, octimibate, melinamide, and SaH 58-035 were all less potent in vivo compared to CI-976 and CL 277,082, and CI-976 produced the greatest decrease in liver cholesteryl esters. Subcutaneous (SC) administration of CI-976 was also efficacious in cholesterol-fed animals. In sucrose-fed rats, oral and SC CI-976 administration potently lowered plasma triglycerides. Hepatic cholesteryl ester accumulation in the ethinyl estradiol-treated rat was also diminished by orally administered CI-976. ACAT activity and cholesteryl ester mass were dose-dependently decreased in the livers from cholesterol-fed rats treated with CI-976, suggesting a direct effect on the liver. In both hypercholesterolemic and hypertriglyceridemic models, CI-976 also decreased plasma apoB concentrations. In other experiments radiolabeled CI-976 accumulated in the liver after multiple doses. Time-dependent changes in biliary lipid and bile acid secretion suggested that free cholesterol did not accumulate in the liver but instead was excreted as such or as bile acid. Finally, inhibition of endogenous and exogenous intestinal cholesterol absorption was demonstrated using several in vivo techniques. The combined data strongly supports the hypothesis that orally administered CI-976 inhibits both intestinal and hepatic ACAT, and that both of these enzymes may be determinants of plasma lipid concentrations in the rat.


Apoptotic cell death in renal injury: the rationale for intervention.
Cell number abnormalities are frequent in renal diseases, and range from the hypercellularity of postinfectious glomerulonephritis to the cell depletion of chronic renal atrophy. Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in the kidney. The potential role of apoptosis ranges from induction and progression to repair of renal injury. Death ligands and receptors, such as tumor necrosis factor and Fas ligand, proapoptotic and antiapoptotic Bcl2 family members and caspases have all been shown to participate in apoptosis regulation in the course of renal cell injury. However, the precise role of these proteins is unclear, and the participation of most known apoptosis regulatory proteins has not been studied. We now review the role of apoptosis in renal injury, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis, with emphasis on the acute tubular necrosis.


A comparison of hepatic sonographic features and histopathologic diagnosis in canine liver disease: 138 cases.
Ultrasound examination is commonly used in the diagnostic evaluation of liver disease in dogs. To determine if hepatic sonographic features were predictive of findings on liver histopathology. We hypothesized that there would be a relationship between sonographic features and the category of liver disease based on histologic assessment. One hundred and thirty-eight dogs in which the liver was evaluated by both abdominal ultrasound examination and histopathologic examination. Twenty-five dogs were included in each of the following categories based on histopathology: normal, degenerative, vascular, inflammatory, and neoplasia. Thirteen dogs had nodular regeneration. Retrospective study. Medical records of dogs from 2005 to 2010 were searched for cases in which the liver was evaluated by abdominal ultrasound examination as well as by histopathology. After independent evaluation of ultrasound images, the recorded sonographic features were analyzed to identify abnormalities associated with each histopathologic diagnosis or degree of fibrosis. Sixty-four percent of sonographically unremarkable livers had histologic abnormalities. Both microhepatia and the identification of abnormal vasculature were significantly associated with a histopathologic diagnosis of vascular disease. Hepatic masses were significantly associated with a diagnosis of neoplasia. Dilated common bile duct and thickened gall bladder wall were significantly associated with hepatitis. There were no sonographic findings consistently present with hepatic fibrosis. Although some ultrasonographic findings, including masses, microhepatia, anomalous veins, and biliary changes, are associated with specific histopathologic abnormalities, sonographic findings are inconsistently detected in many disorders. Overall, hepatic ultrasonographic abnormalities have substantial limitations in predicting the underlying disease.


A kinetic study of guest displacement reactions on a host-guest complex with a photoswitchable calixarene.
The displacement processes of several guests, incorporated in a calixarene host system, were investigated in the gas phase by electrospray ionization-Fourier transform-ion cyclotron resonance (ESI-FT-ICR) mass spectrometry. The complexes resulting from a resorcin[4]arene host with ammonia and sec-butylamine guests were isolated in an ICR-cell, separately using both states of the photoswitch as well as two reference systems for the open and closed forms of the photoswitchable host. The isolated complexes were forced to exchange the guest by using methylamine, ethylamine and sec-butylamine, resulting in different reaction rates for all the measured systems. Especially, the reaction rates of both states of the photoswitch are dependent on the provided guest. Potential side effects like proton exchanges were examined by an H/D-exchange experiment. The results were investigated and supported by quantum chemical calculations (DFT).


Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression.
Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood. Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo. We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1β. Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1β secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.


Inflammatory processes in amyotrophic lateral sclerosis.
Neuroinflammation is a characteristic of pathologically affected tissue in several neurodegenerative disorders. These changes can be observed in the brainstem and spinal cord of amyotrophic lateral sclerosis (ALS) cases and in mouse models of the disease. They include an accumulation of large numbers of activated microglia and astrocytes, as well as small numbers of T cells, mostly adhering to postcapillary venules. Accompanying biochemical alterations include the appearance of numerous molecules characteristic of free-radical attack, the occurrence of proteins associated with activation of the complement cascade, and a sharp upregulation of the enzyme cyclooxygenase 2 (COX-2). Anti-inflammatory agents may have a role to play in treating ALS. COX-2 is a particularly attractive target because of its marked increase in ALS spinal cord.


Glutathione metabolism in lenses of Emory and cataract-resistant mice: activity of five enzymes.
The activities of five enzymes of glutathione metabolism were determined in lenses from cataract-resistant and cataract-prone (Emory) mouse variants at three different ages (5 weeks, 10 weeks and 6 months). The enzymes included those required for glutathione synthesis, gamma-glutamylcysteine synthetase and glutathione synthetase, as well as glutathione-S-transferase, glutathione peroxidase and glutathione reductase. The differences in the activities of the five enzymes in the two mouse variants were not remarkable at any of the three ages. Activity of each enzyme was noted to be in excess of the preceding one in this integrated metabolic pathway, with the exception of glutathione reductase. gamma-Glutamylcysteine synthetase appears to be the pacesetting enzyme of this metabolic scheme in the mouse lens. The activity of each enzyme was compared with that earlier reported for human, rabbit and dog lenses.


Autoinflammatory disease mimicking acute hemorrhagic edema of infancy.
The autoinflammatory diseases are a heterogeneous group of disorders characterized by early appearance of symptoms and characteristic flares of fever plus signs of internal inflammation, including various skin manifestations. We describe a 2.5-year-old boy who presented with fever, purpuric skin lesions, and edema, the classic clinical triad of acute hemorrhagic edema of infancy (AHEI). Although AHEI was our initial leading diagnosis, additional history revealed that these episodes were recurrent, and further investigation lead to a diagnosis of tumor necrosis factor receptor-associated periodic syndrome (TRAPS). This case report affirms the broad clinical spectrum of the autoinflammatory diseases and reinforces the importance of obtaining a thorough history of previous episodes of skin and extracutaneous inflammation in patients with a clinical diagnosis of AHEI.


A chitosan-based multifunctional hydrogel containing in situ rapidly bioreduced silver nanoparticles for accelerating infected wound healing.
Generally, bacterial infection seriously hinders the wound healing process, so it is crucial to safeguard the wound from severe infection. Besides, multifunctional hydrogel dressings (self-healing, injectable, antibacterial and adaptable) seem to be conducive to meet the needs of wound healing. Here, a double-crosslinked multifunctional hydrogel (COC hydrogel) based on quaternized chitosan, methacrylate anhydride-modified collagen and oxidized dextran was developed. The double-crosslinked network improved the stability of the hydrogel while not destroying the functionality of the Schiff base bond. More importantly, silver ions were rapidly in situ bioreduced to silver nanoparticles (AgNPs) during the formation of the COC hydrogel, which can essentially avoid the dispersion and agglomeration problems. The obtained COC@AgNP hydrogel had good biocompatibility compared with that loaded with silver ions and excellent antibacterial properties compared with that loaded with the same amount of commercial AgNPs. In vivo results indicated that the COC@AgNP hydrogel accelerated the healing process of infected full-thickness skin defects through anti-infection, anti-inflammation, stimulating collagen deposition, and promoting the formation of epithelia and blood vessels. Collectively, the COC@AgNP hydrogel has good potential for clinical infected wound dressing applications.


The effects of small doses of barbiturate on the activity of primate nociceptive tract cells.
The activity of neurons identified as or similar to spinothalamic tract cells was compared in anesthetized, intact monkeys and in unanesthetized, decerebrate or spinalized animals. Background activity and responses to A- and C-fiber volleys were smaller in decerebrate than in the other preparations, suggesting the presence of a tonic descending inhibition of nociceptive tract cells in the decerebrate state. Injections of small doses of sodium pentobarbital caused a slight increase in sensitivity of peripheral receptive fields to mechanical stimuli in some cells, and an increase in responses to squeezing the skin with forceps and to C-fiber volleys. Larger doses of pentobarbital reduced the responses to A- and C-fiber volleys. These observations suggest that the activity of nociceptive tract cells is well preserved in the presence of the doses of pentobarbital we routinely use and are consistent with the hyperalgesic state reported to be produced by small doses of barbiturate.


Down regulation of interleukin-1beta-induced nitric oxide production in lacrimal gland acinar cells by sex steroids.
Because the ocular surface is constantly exposed to allergens and irritants, it was reasoned that one cause of dry eye might be damage from inflammatory responses normally regulated by sex steroids. To test this hypothesis, we determined if sex steroids could down regulate nitric oxide (NO) production induced by interleukin-1beta (IL-1beta) in cultured rabbit lacrimal gland acinar cells. Cultured rabbit lacrimal gland acinar cells were exposed to IL-1beta to stimulate NO production. Stimulated cells were treated with different sex steroids and expression of iNOS protein determined by Western blotting and NO production by a nitrate/nitrite colorimetric assay. It was found that the androgens testosterone, dihydrotestosterone, dehydroepiandrosterone and dehydroepiandrosterone-sulfate and 17beta-estradiol were able to inhibit interleukin-1beta-induced NO production in rabbit lacrimal gland acinar cells at physiological concentrations, while progesterone was not able to inhibit NO production. Sex steroid inhibition of NO production was not due to down regulation of iNOS protein production nor was it due to down regulation of GTP cyclohydrolase I with consequent loss of tetrahydrobiopterin production. The results reported here show that androgens and estrogens can down regulate cytokine-mediated responses in cells that are part of the ocular surface protection system and thereby may have an important role in regulating inflammatory responses in the eye. Deficiencies in these steroids, as occurs in postmenopausal women, may lead to damage of the cells responsible for producing the fluids that protect the ocular surface and subsequently to dry eye disease.


Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer.
Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17-3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84-2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21-4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. The results suggest that higher tumor proliferation and motility may be important in the prognosis of NSCLC, and composite application of biomarkers might be of greater value than single marker application in assessing tumor prognosis.


Amplification of CCl4 toxicity by chlordecone: destruction of rat hepatic microsomal cytochrome P-450 subpopulation.
Previous work has established marked amplification of CCl4 hepatotoxicity by prior exposure to chlordecone (CD). Since CCl4 is toxic by virtue of its bioactivation by the hepatomicrosomal cytochrome P-450 (cyt P-450) system, which is in turn destroyed, our first interest was to determine if cyt P-450 isozymes were selectively destroyed in this interaction. CoCl2 also decreased hepatic P-450 contents, so our other interest was to observe whether CoCl2 selectively decreased or spared CCl4 metabolizing P-450 enzymes. Solubilized hepatic microsomes from variously treated rats were used. The treatment protocol was dietary CD (10 ppm, for 15 d), and CCl4 (100 microliters/kg, ip). The treatments were CD alone, CCl4 alone, CD + CCl4 and with or without CoCl2 (60 mg/kg/d, sc for 2 d) treatment on d 13 and 14 of the dietary protocol. The control group received normal diet and corn oil vehicle. The key mixed-function oxidase (MFO) parameters measured were microsomal protein, cyt P-450 content, and aminopyrine demethylase (APD). Decrease of P-450 levels ranged from 2.2-fold (CD + CCl4) to 1.3-fold (CD + CoCl2). APD activity decreased by 48 and 26.6% in CD + CCl4 and CD + CoCl2 treatments, respectively. Using an anion-exchange high-performance liquid chromatography (HPLC) column, solubilized microsomal hemoproteins were resolved into five peaks. The P-450 content associated with each peak was determined. In CD rats there was slight increase in peak heights, whereas peak heights in CCl4 and control treatments were similar. CoCl2 decreased all peaks, the decrease of peak I being maximal. In CD + CCl4 treatment, absence of peaks II and III was noted. Microsomal proteins stained for heme showed decreased staining intensity of hemo-protein bands, particularly band 4 (MW 52,000), which was absent in CD + CCl4 interaction. These findings suggest that (1) CoCl2 does not selectively decrease or spare any P-450 isozymes and (2) CD + CCl4 interaction does destroy specific P-450 isozymes.


Pegylated interferon-alfa-2a monotherapy in patients infected with HCV genotype 2 and importance of rapid virological response.
Pegylated (PEG)-interferon (IFN)-alfa-2a plus ribavirin (RBV) therapy for 24 weeks is now a standard treatment protocol for patients with hepatitis C virus (HCV) genotype 2. As RBV cannot be used in certain situations, we examined whether PEG-IFN-alfa-2a monotherapy for 24 weeks or less would be sufficient to obtain a sustained virological response (SVR) in patients infected with HCV genotype 2. Forty-nine consecutive patients with HCV genotype 2 received PEG-IFN-alfa-2a (180 μg/week) subcutaneously without oral RBV for 8-64 weeks. HCV RNA level was determined by COBAS AMPLICOR HCV Test, v2.0. HCV RNA was equal to or less than 100 KIU/mL (defined as low viral load) in 15 of 49 patients, and the remaining 34 had HCV RNA above 100 KIU/mL (defined as high viral load). All 15 patients with low viral load achieved rapid virological response (RVR; HCV RNA negative at week 4), and also achieved SVR with an average treatment duration of 17.1 weeks. The 34 patients with high viral load were treated for 33.7 weeks on average, and 19 of them (55.9%) achieved RVR. The SVR rates of these patients were significantly higher in those with RVR than without RVR (16/19 vs. 6/15 p = 0.0074). PEG-IFN-alfa-2a monotherapy for 24 weeks or less might be sufficient to treat selected patients with HCV genotype 2, especially those with low viral load and becoming negative for HCV RNA by week 4 of treatment.


Identification and characterization of α1 -antitrypsin in fibrin clots.
Preliminary studies indicated that α1 -antitrypsin (A1AT) is the most abundant protein that is non-covalently bound to fibrin clots prepared from plasma. The aim of this study was to identify and characterize fibrin(ogen)-bound A1AT. Plasma clots were prepared and extensively washed with saline. Clot-bound A1AT could only be extracted using denaturing agents such as urea, thiourea or SDS, pointing to an apparently strong association. Purified fibrinogen, but still containing A1AT as a contaminant, was gel filtered, which showed that the A1AT was bound to fibrinogen. A specific ELISA detected the presence of A1AT-fibrinogen complexes in both purified fibrinogen and pooled normal plasma. Finally, fibrin(ogen)-Sepharose chromatography indicated that A1AT purified from plasma contained a small fraction of fibrin(ogen)-binding A1AT. To study the inhibitory activity of fibrin(ogen)-bound A1AT, both fibrinogen containing A1AT and washed plasma clots were incubated with increasing amounts of elastase. SDS-PAGE and Western blotting showed under both conditions the generation of the A1AT-elastase complex as well as cleaved A1AT. The inhibitory activity of fibrin(ogen)-bound A1AT was also demonstrated by measuring elastase-induced lysis of fibrin clots. Fibrin clots contain strongly bound A1AT, which is functionally active as a serine protease inhibitor (serpin). This A1AT might play a role in the local regulation of proteases involved in coagulation or fibrinolysis and represent a novel link between the inflammatory and hemostatic systems.


Phytochrome properties and the molecular environment.
In vitro data support a scheme of phytochrome phototransformation involving intermediates in a sequential pathway. The fraction of total phytochrome maintained as intermediate under conditions of pigment cycling as well as the rate of the dark reversion of the far red-absorbing (Pfr) to the red-absorbing form of phytochrome (Pr) has been shown to depend on the molecular environment of the phytochrome molecules. Inverse dark reversion of Pr to Pfr has been observed in vitro. These results contribute toward an understanding of the observed paradoxes between physiological experiments and measurements of the amount and state of phytochrome in vivo. The in vivo spectrophotometric assay measures an average of the properties of phytochrome in different cellular environments, whereas a particular physiological response may be controlled by phytochrome molecules in one particular environment. It is therefore possible that all phytochrome is potentially active and triggers specific responses by virtue of its localization.


Cerebral vs. Cardiovascular Responses to Exercise in Type 2 Diabetic Patients.
The human brain is constantly active and even small limitations to cerebral blood flow (CBF) may be critical for preserving oxygen and substrate supply, e.g., during exercise and hypoxia. Exhaustive exercise evokes a competition for the supply of oxygenated blood between the brain and the working muscles, and inability to increase cardiac output sufficiently during exercise may jeopardize cerebral perfusion of relevance for diabetic patients. The challenge in diabetes care is to optimize metabolic control to slow progression of vascular disease, but likely because of a limited ability to increase cardiac output, these patients perceive aerobic exercise to be more strenuous than healthy subjects and that limits the possibility to apply physical activity as a preventive lifestyle intervention. In this review, we consider the effects of functional activation by exercise on the brain and how it contributes to understanding the control of CBF with the limited exercise tolerance experienced by type 2 diabetic patients. Whether a decline in cerebral oxygenation and thereby reduced neural drive to working muscles plays a role for "central" fatigue during exhaustive exercise is addressed in relation to brain's attenuated vascular response to exercise in type 2 diabetic subjects.


Synchrotron white-beam X-ray topography of ribonuclease S crystals.
With careful experimental design, indexed synchrotron white-beam X-ray topographs of ribonuclease S crystals at ambient temperature could be recorded with a definition and contrast comparable to that of monochromatic beam topographs of other proteins reported in the literature. By excluding wavelengths longer than 1 A from the white beam with a filter, a radiation dose equivalent to that required to record about 18 topographs could be tolerated without appreciable radiation damage to the samples. Bragg angles of 0.5 degrees or less were required to select low-index harmonically pure reflections with high intensities and extinction lengths only several times the sample's thickness. The resulting X-ray topographs in some cases showed topographic detail and in others showed the even featureless background that has been considered characteristic of a protein crystal of low mosaicity. The ribonuclease S crystals were well ordered single crystals of a quality comparable to other protein crystals that have been studied by X-ray topography.


Electronic interactions in the expanded metal compound Li-NH3.
Inelastic x-ray scattering was used to measure the plasmon as a function of electron density in liquid lithium ammonia as well as the low temperature solid phase. As the electronic density is lowered, electronic correlation effects cause the random-phase approximation (RPA) to break down, requiring more advanced theoretical treatments. The deviation from RPA becomes greatest at the lowest electronic densities. We also see evidence for decreased electronic screening as shown by an increase in the strength of the pseudopotential at lower concentrations. Plasmon behavior in the solid is similar to that of the heavier alkali metals, but surprisingly different than in the liquid.


Prostaglandin I₂promotes the development of IL-17-producing γδ T cells that associate with the epithelium during allergic lung inflammation.
γδ T cells rapidly produce cytokines and represent a first line of defense against microbes and other environmental insults at mucosal tissues and are thus thought to play a local immunoregulatory role. We show that allergic airway inflammation was associated with an increase in innate IL-17-producing γδ T (γδ-17) cells that expressed the αEβ7 integrin and were closely associated with the airway epithelium. Importantly, PGI(2) and its receptor IP, which downregulated airway eosinophilic inflammation, promoted the emergence of these intraepithelial γδ-17 cells into the airways by enhancing IL-6 production by lung eosinophils and dendritic cells. Accordingly, a pronounced reduction of γδ-17 cells was observed in the thymus of naive mice lacking the PGI(2) receptor IP, as well as in the lungs during allergic inflammation, implying a critical role for PGI(2) in the programming of "natural" γδ-17 cells. Conversely, iloprost, a stable analog of PGI(2), augmented IL-17 production by γδ T cells but significantly reduced airway inflammation. Together, these findings suggest that PGI(2) plays a key immunoregulatory role by promoting the development of innate intraepithelial γδ-17 cells through an IL-6-dependent mechanism. By enhancing γδ-17 cell responses, stable analogs of PGI(2) may be exploited in the development of new immunotherapeutic approaches.


Macrophages in developing mammalian skeletal muscle: evidence for muscle fibre death as a normal developmental event.
Macrophages in the diaphragm of fetal, growing and adult rats were investigated using electron microscopy. In addition, frozen sections of the diaphragm, muscles of the anterior abdominal wall and muscles of the calf were stained for acid phosphatase activity and examined with the light microscope. Macrophages were frequently observed in the muscles at 20 days of gestation and until the animals were 2 weeks old. They were less frequently found in the 4-week-old rats and very rarely found in the 8-week-old and adult rats. They were found in intimate contact with, sometimes apparently surrounding, certain muscle fibres which were very electron dense and considered to be degenerating. In addition, myofibrils were found as phagosomes within the macrophage cytoplasm. There was evidence to support the theory that macrophages develop from mesenchymal cells in embryonic tissue. Cells considered to be early macrophages and containing small lysosomes were found in the muscles at 16 and 18 days of gestation. In all other respects these cells resembled mesenchymal cells. It is proposed that cell death may be a normal developmental event in skeletal muscle, in which macrophages play an important role in the removal of the dead fibres.


Deletion of 2p: a cytogenetic and clinical update.
The locus for acid phosphatase (ACP1) had been alternately assigned to two conflicting regions on the short arm of chromosome 2. We present a clinical and cytogenetic report of one patient who has an interstitial deletion of 2, del(2) (p23p25.1), and a cytogenetic study of another cell line with an interstitial deletion of 2p (p23.1p25.1). Because both patients are heterozygotes for ACP1, the assignment of ACP1 to 2p25.1----pter is supported.


[Mechanisms of the effect of allopurinol on the metabolism of adenine nucleotides].
The effect of repeated administration of allopurinol (50 mg.kg-1 48, 24, and 4 hours before analysis) on the activity of enzymes of degradation and resynthesis of adenine nucleotides was studied. The activity of xanthine dehydrogenase and xanthine oxidase was inhibited in the heart, liver and kidney and the activity of membrane-bound 5'-nucleotidase was particularly elevated in the heart and brain, suggesting that membrane transport processes may be affected. The increase in the activity of hypoxanthine guanine phosphoribosyl transferase in the liver is indicative of a potential mechanism of positive action of allopurinol upon restoring the purine nucleotide store. The authors present their hypothesis on the mechanism of allopurinol action upon the metabolism of adenine nucleotides. The suggested mechanisms might become operative in protecting tissues against ischemia and reperfusion induced damage.


Antimicrobial and Cytotoxicity Activities of Medicinal Plants against Salmonella gallinarum Isolated from Chickens.
Medicinal plants have been the good source of treatment for different ailments of humans as well as animals for centuries. However, in Tanzania, few plants were investigated for their efficacy against various diseases of chickens. In the present study, four medicinal plants were investigated against Salmonella gallinarum isolated from chickens. The minimum inhibitory concentration (MIC) using the broth microdilution methods and minimum bactericidal concentration (MBCs) were used to evaluate the activities of plants against chicken salmonellosis. For the safety of chickens against the toxicity of plants, the cytotoxicity assay was determined using a brine shrimp lethality test. Aloe secundiflora leaf ethyl acetate (ALEA), Aloe rabaiensis leaf methanolic (ArM), Aloe rabaiensis leaf ethyl acetate (ArLEA), and Punica granatum leaf ethyl acetate (PGLEA) extracts exhibited the highest MIC (0.3906 mg/mL) and MBC (3.125 mg/mL), respectively. The Dolichos kilimandscharicus tuber ethyl acetate (DTEA) and Dolichos kilimandscharicus tuber pet ether (DTPE) extracts displayed MIC of 1.563 mg/mL and 12.50 mg/mL and MBC of 12.50 mg/mL and 25.50 mg/mL, respectively. The highest LC50 values exhibited in Dolichos kilimandscharicus ranged from 7.937 × 10-4 mg/mL to 7.242 × 10-2 mg/mL for pet ether and methanolic extracts, respectively, while ALEA extract exhibited LC50 of 7.645 × 10-3 mg/mL. Generally, the extracts with MIC 0.3906 mg/mL and MBC 3.125 mg/mL demonstrated the highest antibacterial activity with low toxicity efficient to manage chicken salmonellosis. Dolichos kilimandscharicus, which exhibited higher toxicity, warrants further investigation on insecticidal and anticancer agents.


Identification of New Genes Involved in Germline Predisposition to Early-Onset Gastric Cancer.
The genetic cause for several families with gastric cancer (GC) aggregation is unclear, with marked relevance in early-onset patients. We aimed to identify new candidate genes involved in GC germline predisposition. Whole-exome sequencing (WES) of germline samples was performed in 20 early-onset GC patients without previous germline mutation identified. WES was also performed in nine tumor samples to analyze the somatic profile using SigProfilerExtractor tool. Sequencing germline data were filtered to select those variants with plausible pathogenicity, rare frequency and previously involved in cancer. Then, a manual filtering was performed to prioritize genes according to current knowledge and function. These genetic variants were prevalidated with Integrative Genomics Viewer 2.8.2 (IGV). Subsequently, a further selection step was carried out according to function and information obtained from tumor samples. After IGV and selection step, 58 genetic variants in 52 different candidate genes were validated by Sanger sequencing. Among them, APC, FAT4, CTNND1 and TLR2 seem to be the most promising genes because of their role in hereditary cancer syndromes, tumor suppression, cell adhesion and Helicobacter pylori recognition, respectively. These encouraging results represent the open door to the identification of new genes involved in GC germline predisposition.


The phylogenetic significance of peptidoglycan types: Molecular analysis of the genera Microbacterium and Aureobacterium based upon sequence comparison of gyrB, rpoB, recA and ppk and 16SrRNA genes.
The type strains of 27 species of the genus Microbacterium, family Microbacteriaceae, were analyzed with respect to the phylogeny of the housekeeping genes coding for DNA gyrase subunit B (gyrB), RNA-polymerase subunit B (rpoB), recombinase A (recA) and polyphosphate kinase (ppk). The resulting gene trees were compared to the 16S rRNA gene phylogeny of the same species. The topology of neighbour-joining and maximum parsimony phylogenetic trees based upon nucleic acid sequences and protein sequences of housekeeping genes differed among each other and no gene tree was identical to that of the 16S rRNA gene tree. Only some species showed consistent clustering by all genes analyzed, but the majority of species branched with different neighbours in most gene trees. The failure to phylogenetically cluster type strains into two groups based upon differences in the amino acid composition of peptidoglycan on the basis of 16S rRNA gene sequence similarity, once leading to the union of the genera Microbacterium and Aureobacterium, was also seen in the analysis of recA, rpoB and gyrB gene and protein phylogenies. Analysis of the pkk gene and protein as well as of a concatenate tree, combining sequences of all five genes (total of 3.700 nucleotides), sees members of the former genus Aureobacterium and other type strains with lysine as diagnostic diamino acid to form a coherent cluster that branches within the radiation of Microbacterium species with ornithine in the peptidoglycan.


Colocolonic intussusception secondary to juvenile polyp, case report.
Colocolonic intussusception is a rare event because the descending colon lies fixed in the retroperitoneal position. We present a ease of colocolonic intussusception in a 17-year-old boy due to multiple juvenile polyps. The patient was treated by left hemicolectomy.


Evaluation of a model of long-term memory based on the properties of the Ca2+/calmodulin-dependent protein kinase.
1.) This paper further explores the feasibility of a model for long-term memory (Lisman, 1985; Lisman and Goldring, 1988). According to this model, the value of synaptic efficacy of individual synapses is stored locally by the group of Ca2+/calmodulin-dependent protein kinase II molecules contained within the post-synaptic density. 2.) Calculations presented in a previous paper indicate that it is feasible for these kinase molecules to encode information with the stability required for long-term memory. These calculations were based on the assumption that the 30 phosphorylation sites on the enzyme are phosphorylated in a serial fashion, i.e. that the sites are not independent. This paper presents similar calculations based on the alternative assumption that the sites are phosphorylated independently. 3.) Kinase molecules that have been switched "on" undergo a continuous process of dephosphorylation and rephosphorylation. Estimates of the energy consumed by this cycle indicate that the energy required would not make unreasonable demands on neuronal metabolism. The necessity of energy consumption by molecular switches is discussed. 4.) The rate of intramolecular autophosphorylation of the Ca2+/calmodulin dependent kinase implies that the cytoplasmic free Ca2+ concentration must stay elevated for several seconds in order for kinase molecules to switch "on". How such a sustained rise in Ca2+ might be achieved is discussed. 5.) An alternative view is that long-term memory storage involves a change in gene expression. The principal evidence supporting this view is the effect of protein synthesis inhibitors on memory. A model is presented showing that the observed effect of protein synthesis inhibitors does not necessarily imply that information storage is at the level of gene expression. 6.) The distinction between "presynaptic" and "postsynaptic" associative learning mechanisms is discussed. It is concluded that this distinction can be misleading and that the possibility that the underlying mechanisms are similar should not be excluded.


Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?
Recently, cervical cancer rates elevation has been noted in women aged 20-39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25-29 years, which should necessitate effective precancer screening in younger age groups, including those <25 years. From 30.066 liquid-based screening tests results (n = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women <30 years were selected. Performance characteristics were calculated for three screening models: primary HRHPV with p16/Ki67 triage, primary cytology with reflex HPV and primary cytology alone. Primary HRHPV with p16/Ki67 triage was significantly more sensitive in high-grade squamous intraepithelial lesion quantified with cervical intraepithelial neoplasia grade 2 or worse [HSIL(CIN2+)] detection than cytology with reflex HRHPV and cytology alone (83.3% vs. 70.8%/45.8%) and had significantly higher diagnostic predictive values (PPV:29.4%/21.3%/22.9%; NPV:91.7%/82.9%/82.2%, respectively at CIN2+ threshold). The number of colposcopies per HSIL(CIN2+) detection indices was 3.4, 4.7 and 4.4, respectively. Primary HPV testing in women <30 years with p16/Ki67 triage of HPV-positive cases might be an effective cervical cancer screening strategy for HSIL(CIN2+) detection with superior diagnostic performance when compared with primary cytology-based models. Women <25 years might also benefit from an introduction to a more sensitive screening approach.


A Randomized Controlled Trial of Group Triple P With Chinese Parents in Mainland China.
This study evaluated the effects of Group Triple P with Chinese parents on parenting and child outcomes as well as outcomes relating to child academic learning in Mainland China. Participants were 81 Chinese parents and their children in Shanghai, who were randomly allocated to an intervention group or wait-list control group. Parents in the intervention condition received Group Triple P training, and parents and children were assessed at three/two time points. Compared with the control group, parents in the intervention group reported significant improvements in child adjustment problems, parenting practices, parental adjustment, and parenting self-efficacy at post-assessment. Moreover, there was a significant increase in parents' satisfaction with children's academic achievement and a reduction in children's academic problem behaviors at post-intervention. All these effects were maintained at 6-month follow-up. There was also a significant increase in the child report of positive parenting at post-intervention.


Effect of substrate on radiative properties of thin films.
An expression for the directional transmittance of an absorbing thin film on anabsorbing substrate was developed by using the classical electromagnetic theory. This expression when combined with the wellstudied reflectance can yield absorptance values that are of utmost interest in heat transfer studies. The behavior of the normal and hemispherical reflectance, absorptance, and transmittance is exhibited for some selected values of film and substrate optical constants and is presented graphically as a function of film optical thickness. The results indicate that the imaginary part of the complex index of refraction for both film and substrate should be accounted for when calculating radiative transfer and properties of such films.


High-Photovoltage Silicon Nanowire for Biological Cofactor Production.
Photocathodic conversion of NAD+ to NADH cofactor is a promising platform for activating redox biological catalysts and enzymatic synthesis using renewable solar energy. However, many photocathodes suffer from low photovoltage, consequently requiring a high cathodic bias for NADH production. Here, we report an n+p-type silicon nanowire (n+p-SiNW) photocathode having a photovoltage of 435 mV to drive energy-efficient NADH production. The enhanced band bending at the n+/p interface accounts for the high photovoltage, which conduces to a benchmark onset potential [0.393 V vs the reversible hydrogen electrode (VRHE)] for SiNW-based photocathodic NADH generation. In addition, the n+p-SiNW nanomaterial exhibits a Faradaic efficiency of 84.7% and a conversion rate of 1.63 μmol h-1 cm-1 at 0.2 VRHE, which is the lowest cathodic potential to achieve the maximum productivity among SiNW-sensitized cofactor production.


Some Recommendations on the Use of Daily Life Methods in Affective Science.
Real-world emotions are often more vivid, personally meaningful, and consequential than those evoked in the lab. Therefore, studying emotions in daily life is essential to test theories, discover new phenomena, and understand healthy emotional functioning; in short, to move affective science forward. The past decades have seen a surge of research using daily diary, experience sampling, or ecological momentary assessment methods to study emotional phenomena in daily life. In this paper, we will share some of the insights we have gained from our collective experience applying such daily life methods to study everyday affective processes. We highlight what we see as important considerations and caveats involved in using these methods and formulate recommendations to improve their use in future research. These insights focus on the importance of (i) theory and hypothesis-testing; (ii) measurement; (iii) timescale; and (iv) context, when studying emotions in their natural habitat.


Describing Activity in Primary Percutaneous Coronary Intervention: An Exploration of Denominators. From the HEAT Trial - A Systematic Evaluation of PPCI Activations in Liverpool, Explaining Denominators (HEAT-SEALED).
The provision of primary percutaneous coronary intervention (PPCI) in the emergency management of ST-elevation myocardial infarction (STEMI) is expensive and resource intensive. Accurate data collection is essential not only for outcomes analysis but also to characterize activity and performance for regions, centers, and operators. Inconsistency in the use of denominators currently creates problems in data interpretation. To establish a system of denominator groupings, seeking to better describe the range of clinical activity resulting from an unselected series of PPCI activations. The HEAT-SEALED pathway designates a key denominator group (n1-n9) to each phase of PPCI activity and identifies a final "destination category" for each patient leaving the pathway. HEAT-PPCI (How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention) is a true "all-comers" trial and provides an ideal platform to collect data for prospective validation of the pathway. We report data from all PPCI activation events for the HEAT-PPCI trial. Our findings demonstrate important differences between the sizes of key PPCI denominator groups and hence the potential for variation in reported outcomes depending on the denominator category selected. The main figures are: all activations (n1 = 2490); all suspected MI cases (n4 = 1940; 77.91%); patients in whom angiography was performed (n5 = 1904; 76.46%); cases in which diagnosis was confirmed with a probable culprit lesion (n6 = 1657; 66.54%), and cases with complete PCI success (n9 = 1441; 57.87%). The HEAT-SEALED pathway offers a practical and comprehensive solution to the problem of describing denominators in STEMI and PPCI. Routine application would facilitate a more consistent and precise description of activity and outcome.


Biotic elicitation of the Trifolium pratense L. suspension culture.
The important substances of secondary metabolism include flavonoids and isoflavonoids. The Trifolium pratense L. (Fabaceae) suspension culture's yield of these metabolites is low, thus an attempt was made to increase the production by elicitation. The endogenous signal substances of the plants' defensive responses include jasmonic acid that also functions as a biotic elicitor in the case of exogenous application. In the experiment the authors monitored the impact of 4 different concentrations of jasmonic acid on the Trifolium pratense L. (variety DO-8 and variety DO-9) suspension culture's yield. The culture was cultivated in Gamborg medium to which 2 mg.l(-1) of 2,4-dichlorophenoxyacetic acid and 2 mg.l(-1) of 6-benzylaminopurine were added. The maximum increase in the production of flavonoids was achieved, when compared with the control samples, with both varieties of the 500 micromol concentration (DO-9, 6-hour application by 140%; DO-8, 24-hour application by 65%). The production of isoflavonoids (genistin, daidzein, genistein, and formononetine) was best stimulated in both varieties by the 50 micromol concentration (in the case of DO-9 variety, the 48-hour application increased the content of genistin by up to 845%).


Repetition suppression and repetition priming are processing outcomes.
Abstract There is considerable evidence that repetition suppression (RS) is a cortical signature of previous exposure to the environment. In many instances RS in specific brain regions is accompanied by improvements in specific behavioral measures; both observations are outcomes of repeated processing. In understanding the mechanism by which brain changes give rise to behavioral changes, it is important to consider what aspect of the environment a given brain area or set of areas processes, and how this might be expressed behaviorally.


[The epidemiology and risk factors of ischemic cardiopathy].
The prevention of cardiovascular diseases has been considered the first cause in diminishing coronary heart disease mortality. The main objective is the control of risk factors in primary as well as in secondary prevention. The correlation between diet rich in saturated fat and plasma cholesterol was the first milestone in this field followed by the improvement in cholesterol levels and subsequently in CHD mortality. Smoking cessation, physical exercise and control of blood pressure have shown to be efficacious. May be that Syndrome X that corresponds to insulin resistance, central obesity and low levels of HDL among other characteristics, reaches in the future a greater importance in CVD epidemiology. Other risk factors like those of psychosocial origin, thrombogenesis or hormones need more research in order to know their actual importance.


Leptin and its association with polycystic ovary syndrome: a twin study.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy with symptoms such as obesity, insulin resistance and hyperandrogenemia. PCOS might be the result of a genetic disorder. Genetic discrepancy in the production of leptin, a product of the obesity gene, may lead to various endocrinopathies such as PCOS. The objective of this study was first, to ascertain the incidence of PCOS, using the gold standard; second, to ascertain the genetic property of leptin; and third, to evaluate the association between leptin concentration and PCOS. A total of 154 Tehran-resident female-female twins were studied. They included 48 pairs of monozygotic (MZ) and 29 pairs of dyzygotic (DZ) twins, aged 15-45 years. Clinical, ultrasound and biochemical findings were used to diagnose PCOS. The incidence of PCOS using biochemical and clinical features was 16.2%. The correlation coefficient between serum leptin levels of MZ twins was higher than that of the DZ twins. The serum level of leptin was similar between subjects with or without PCOS, irrespective of their zygosity. It was concluded that the incidence of PCOS is high among twins, and that leptin is likely to be genetically determined, although the effect of environmental factors cannot be denied. This study did not find any association between the diagnosis of PCOS and leptin level. However, the link between the two may lie with other entities such as eating disorders and/or obesity.


The International Sexual Health And REproductive Health during COVID-19 (I-SHARE) Study: A Multicountry Analysis of Adults from 30 Countries Prior to and During the Initial Coronavirus Disease 2019 Wave.
There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium. Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence. Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.


Heterogeneities in the latent functions of employment: New findings from a large-scale German survey.
Building on social psychologist Marie Jahoda's pioneering work, the psychological literature has shown that work fulfills both manifest functions (e.g., monetary returns) and latent functions (e.g., social contact). This article uses data from the German panel study "Labor market and social security" (PASS), which contains information on latent and manifest factors (from a shortened latent and manifest benefits, or LaMB, scale), as well as a large array of other variables for over 9,000 respondents. This probability-sampled data allowed for detailed analyses that have not been previously possible. We investigate differences in these factors by labor market status, among those employed, and among those unemployed. We identify considerable variation between status groups, suggesting that employment, overall, is important and that longer periods of unemployment lead to a gradual decay of the latent and manifest factors. Furthermore, regression analyses show that the LaMB measures account for approximately 70% of the partial correlations between unemployment and various well-being measures.


Effects of rapeseed-press cake glucosinolates and iodine on the performance, the thyroid gland and the liver vitamin A status of pigs.
Rapeseed press cake (per kg DM 181 g EE, 341 g CP and 23.3 mmol glucosinolates) was tested in a long-term experiment with a total of sixty pigs (live weight range 24 to 104 kg). The 3 x 2 factorial design consisted of three rapeseed press cake levels (no rapeseed press cake--control, 75 g or 150 g rapeseed press cake per kg diet) each with two iodine dosages (125 or 250 micrograms supplementary iodine per kg diet). Reduced feed intake and depressed weight gain were found in groups receiving 150 g rapeseed press cake per kg diet, which correspond to 3.2 mmol glucosinolates per kg diet. At an inclusion level of 75 g rapeseed-press cake per kg diet no differences in feed intake and growth intensity were recorded in comparison to the rape feed free control. The rapeseed-press cake diet increased the weight of thyroid gland and liver and decreased the serum thyroxine (T4) concentration. Higher iodine dosage increased the serum T4 concentration of pigs receiving 75 g rapeseed press cake per kg diet (= 1.6 mmol glucosinolates per kg diet) to the level of the control group and retarded the enlargement of the thyroid gland. Intake of rapeseed products lowered the iodine content of the thyroid gland, however, there was no significant difference between groups given 1.6 and 3.2 mmol glucosinolates per kg diet. The vitamin A content of the whole liver and the vitamin A serum concentration were not influenced by the diets tested. However, rapeseed press cake and the glucosinolates, respectively, decreased the vitamin A concentration per gram liver due to the organ enlargement and the resulting dilution effect.


[Using Delphi method to establish diagnostic standard for Xin-blood stasis syndrome].
To provide a reference for quantitative diagnosis of Xin-blood stasis syndrome (XBSS) by way of collecting experiences from experts, screening out the diagnostic indices and evaluating their significance. With Delphi method adopted, two rounds of questionnaire survey were carried out in 20 experts, the feedback data were statistically analyzed in terms of concentricity, coordination and authority using SPSS software. The recovery rates of the two round survey were all 100%; the coordinate coefficient was 0.658 in the first round and 0.622 in the second. And results passed the Chi-square test with P < 0.05, Chi2 = 189.544 in first round and 235.232 in second round. The average degree of expert's authority was 85%. The enthusiasm and speciality of the 20 experts were high, and their opinions are of high reliability with great coordination. The information entries, including chest pain, stabbing pain, pain on a relatively fixed position, chest stuffiness, ecchymosis or petechia on tongue, dark-purplish lip and unsmooth pulse, can be taken as the diagnostic indices for XBSS sydrome.


The new fundamentals in nursing: introducing beginning quality and safety education for nurses' competencies.
This article describes the redesign of the fundamentals of nursing course using an organizing framework and teaching strategies identified in the Quality and Safety Education for Nurses (QSEN) initiative. Six QSEN competencies (patient-centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics) are essential for nursing practice. Beginning knowledge, skills, and attitudes (KSAs) associated with each competency were identified in a preliminary Delphi survey as important to incorporate early in prelicensure nursing curricula. Redesign requires a shift in focus from task-training and psychomotor skills development to incorporation of a systems context, reflecting redefined values and interventions associated with safety, quality, and professional nursing roles. A course revision, based on the QSEN competencies definitions, selected beginning KSAs, exemplar resources, and teaching strategies, is described. The reframing of fundamentals of nursing is essential to prepare new graduates for contemporary practice.


Treatment for intermittent claudication and the effects on walking distance and quality of life.
The objective of the study was to provide an overview of the most common treatments for intermittent claudication and to determine the effectiveness in improving walking distance and quality of life based on a combination of direct and indirect evidence. We included trials that compared: angioplasty, surgery, exercise therapy or no treatment for intermittent claudication. Outcome measurements were walking distance (maximum, pain-free) and quality of life (physical, mental). We used a network meta-analysis model for the combination of direct and indirect evidence. We included 42 studies, presenting 3106 participants. The network meta-analysis showed that supervised exercise therapy (Δ = 1.62, P < 0.01), angioplasty (Δ = 1.89, P < 0.01) and surgery (Δ = 2.72, P = 0.02) increased walking distance significantly more than no treatment. Furthermore, supervised exercise therapy (Δ = 0.60, P < 0.01), angioplasty (Δ = 0.91, P = 0.01) and surgery (Δ = 1.07, P < 0.01) increased physical quality of life more than no treatment. However, in the sensitivity analysis, only supervised exercise therapy had additional value over no symptomatic treatment (Δ = 0.66, P < 0.01). In conclusion, this network meta-analysis indicates that supervised exercise therapy is more effective in both increasing walking distance and physical quality of life, compared with no treatment. Angioplasty and surgery also increase walking distance, compared with no treatment, but results for physical quality of life are less convincing.


[Epidemic analysis of HIV-1 incidence using BED-CEIA assay in Tianjin, China, 2010].
To explore the epidemic characteristics of HIV-1 recent infection among high-risk populations in Tianjin and to provide reasonable evidence for intervention strategy. Blood samples were detected using BED-CEIA to identify recent HIV-1 infection, and HIV/AIDS cases in Tianjin 2010 were collected to analyze epidemic data. 349 of reported HIV/AIDS cases were confirmed from total 777 207 people. ALL of 87 HIV-1 recent infections were males and mainly detected from men who have sex with men (MSM), voluntary counseling and testing (VCT) and STD outpatients, the HIV-1 incidence of each group was 1.48%, 0.38%, 0.17% respectively. There were not significant difference in recent HIV-1 infection rate between other areas and locals. The homosexual transmission was 80.46% among recent HIV-1 infections. The results of this study showed that the homosexual contact was primary route of HIV transmission in Tianjin. The infection of HIV was serious among MSM, effective interventions should be taken for HIV/AIDS control and prevention urgently.


[A 3-hour period ultradian rhythm of the sleep-wakefulness cycle and growth hormone secretion in the immature rat].
The temporal patterns of the sleep-wakefulness cycle and growth hormone secretion throughout a day in the male and female rat were studied in male and rats at 27 approximately 31 days of age. EEGs were recorded continuously from 27 to 31 days of age, and a time series of the amount of sleep for every 10 min was obtained. Serial blood sampling through an intracardiac cannula at 10-min intervals was performed for each of the 6-h periods beginning at 12:00, 18:00, 00:00 and 06:00 h. By analysis of the power spectrum and the least squares method, the time series was found to have approximately a 3.0-h periodicity in any of the 6-h periods and in either sex. The peak time which was estimated for the time series of GH concentrations was found to occur consistently around 02:00 approximately 03:00, 05:00 approximately 06:00, 08:00 approximately 09:00, 11:00 approximately 12:00, 14:00 approximately 15:00, 17:00 approximately 18:00, 20:00 approximately 21:00 and 23:00 approximately 24:00 h in either the male or the female rat. The time series of the amount of sleep over a 24-h period at 29 days of age revealed an ultradian rhythm with approximately a 3.0-h periodicity, and the peak time was estimated to be the same as that for the GH time series Taking the findings that the GH secretion is related to sleep in the prepubertal rat as described in the accompanying paper (Tsai, 1983), it could be speculated that the rat GH secretory rhythm develops by 30 days of age as a 3.0-h period ultradian rhythm that entrains to the time of day, relating to the rhythm of the sleep-wakefulness cycle.


Use of electronic cigarettes among state tobacco cessation quitline callers.
Little is known about the prevalence of electronic cigarette (e-cigarette) use among tobacco users who seek help from state tobacco quitlines, the reasons for its use, and whether e-cigarettes impact a user's ability to successfully quit tobacco. This study investigates these questions and describes differences among state quitline callers who used e-cigarettes for 1 month or more, used e-cigarettes for less than 1 month, or never tried e-cigarettes. Data on e-cigarette use were collected from 2,758 callers to 6 state tobacco quitlines 7 months after they received intervention from the quitline program. Nearly one third (30.9%) of respondents reported ever using or trying e-cigarettes; most used for a short period of time (61.7% for less than 1 month). The most frequently reported reasons for use were to help quit other tobacco (51.3%) or to replace other tobacco (15.2%). Both e-cigarette user groups were significantly less likely to be tobacco abstinent at the 7-month survey compared with participants who had never tried e-cigarettes (30-day point prevalence quit rates: 21.7% and 16.6% vs. 31.3%, p < .001). Demographic differences between the 3 groups are discussed. This study offers a preliminary look at e-cigarette use among state quitline callers and is perhaps the first to describe e-cigarette use in a large group of tobacco users seeking treatment. The notable rates of e-cigarette use and use of e-cigarettes as cessation aids, even though the U.S. Food and Drug Administration has not approved e-cigarettes for this purpose, should inform policy and treatment discussions on this topic.


Calcium antagonists and tissue protection.
The tissue-protective effect of the calcium antagonists is a complex phenomenon that needs to be considered at the cellular as well as the organ level, and with respect to both the vasculature and myocardium. As far as the vasculature and the myocardium are concerned, hypertension is a major risk factor. The dihydropyridine-based calcium antagonists are protective under these circumstances, not only because of their blood pressure-lowering effect but also because of their ability to slow plaque formation and possibly to provide some protection against oxyradical-induced injury. With regard to the myocardium, tissue protection in the presence of hypertension involves not only a reduction in hypertrophy, but also a reduction in ischemia-induced injury and the incidence of damage due to lipid peroxidation.


Hypoplastic Left Ventricle: Hypoplastic Left Heart Complex.
Hypoplastic left heart syndrome (HLHS) without intrinsic valvar stenosis or atresia is synonymous with the term hypoplastic left heart complex (HLHC) and is defined as a cardiac malformation at the milder end of the spectrum of HLHS with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle and hypoplasia of the aortic or mitral valve, or both valves, in the absence of intrinsic valvar stenosis or atresia, and with hypoplasia of the ascending aorta and aortic arch. This article describes the definitions, nomenclature, and classification of HLHC; the indications and contraindications for biventricular repair of HLHC; the surgical treatment of HLHC; and the associated outcomes.


Boning up on ephrin signaling.
The activities of osteoclasts, which degrade bone, and osteoblasts, which form bone, are coordinated to maintain bone homeostasis. Zhao et al. (2006) now demonstrate bidirectional signaling between these two cell populations via the transmembrane ligand ephrinB2 expressed by osteoclasts and its receptor EphB4 expressed by osteoblasts. Such bidirectional signaling limits osteoclast activity while stimulating osteoblast differentiation.


Driving Under the Influence: How Music Listening Affects Driving Behaviors.
Car driving is a daily activity for many individuals in modern societies. Drivers often listen to music while driving. The method presented here investigates how listening to music influences driving behaviors. A driving simulation was selected because it offers both a well-controlled environment and a good level of ecological validity. Driving behaviors were assessed through a car-following task. In practice, participants were instructed to follow a lead vehicle as they would do in real life. The lead vehicle speed changed over time requiring constant speed adjustments for the participants. The inter-vehicular time was used to assess driving behaviors. To complement the driving behaviors, the subjective mood and physiological level of arousal were also collected. As such, the results collected using this method offer insights on both the human internal state (i.e., subjective mood and physiological arousal) and driving behaviors in the car following task.


The Potential Role of iNOS in Ovarian Cancer Progression and Chemoresistance.
Inducible nitric oxide synthase (iNOS), the enzyme responsible for nitric oxide (NO) production, is not present in most cells under normal conditions. The expression of its mRNA, as well as its protein synthesis and full enzymatic activity, undergoes multilevel regulation including transcriptional and posttranscriptional mechanisms, the availability of iNOS substrate and cofactors and oxygen tension. However, in various malignant diseases, such as ovarian cancer, the intracellular mechanisms controlling iNOS are dysregulated, resulting in the permanent induction of iNOS expression and activation. The present review summarizes the multistaged processes occurring in normal cells that promote NO synthesis and focuses on factors regulating iNOS expression in ovarian cancer. The possible involvement of iNOS in the chemoresistance of ovarian cancer and its potential as a prognostic/predictive factor in the course of disease development are also reviewed. According to the available yet limited data, it is difficult to draw unequivocal conclusions on the pros and cons of iNOS in ovarian cancer. Most clinical data support the hypothesis that high levels of iNOS expression in ovarian tumors are associated with a greater risk of disease relapse and patient death. However, in vitro studies with various ovarian cancer cell lines indicate a correlation between a high level of iNOS expression and sensitivity to cisplatin.


[Evaluation of secular trend of liver cancer incidence in Qidong, Jiangsu province, 1973-2002].
To evaluate the secular trend of liver cancer incidence 1973-2002 in Qidong, a high-prevalent area in Jiangsu province. The population-based cancer registration data collected during the period of 1973-2002 were used to calculate the crude rate (CR), world age-standardized rate (WASR), five-year age-specific rate, truncated rate of those aged 35-64, cumulative rates of those aged 0-64 and 0-74, percent change (PC), and annual percent change (APC). The incidence rates by age, period/age, and cohort/age were analyzed and compared. The CR was 59.28 per 100,000 on average; and was 91.65 per 100,000 for males and 27.64 per 100,000 for females, with a sex ratio of 3.32:1. The WASR was 58.71 per 100,000 on average; and was 93.32 per 100,000 for males and 26.46 per 100,000 for the females. The truncated rate and cumulative rate of those aged 0-64 and 0-74 were 143.61 per 100,000 and 4.74% and 6.07% respectively. The PC and the APC were +30.90% and +1.58% for the crude incidence rate, and +12.33% and +0.41% for the age-standardized rate. The incidence data demonstrated a rising trend in general and a decreasing pattern for the age-specific rates under age of 35 by comparing the two 15-year periods. Decline trend also existed for the younger age groups when the time was divided into 6 subperiods. Birth cohort analysis showed notable reducing changes for those born after the year 1963. The crude rate of incidence of liver cancer has arisen in general in the past 30 years in Qidong area, which may reflects the increase of middle-aged and elderly populations. Many years' comprehensive prevention measures taken in the area, however, have been and will continue to be effective on the decrease of the incidence of liver cancer among the younger generations.


The Association between Health Conditions in World Trade Center Responders and Sleep-Related Quality of Life and Sleep Complaints.
Background: World Trade Center (WTC) dust-exposed subjects have multiple comorbidities that affect sleep. These include obstructive sleep apnea (OSA), chronic rhinosinusitis (CRS), gastroesophageal-reflux disorder (GERD) and post-traumatic stress disorder (PTSD). We examined the impact of these conditions to sleep-related outcomes. Methods: Demographics, co-morbidities and symptoms were obtained from 626 WTC (109F/517M), 33⁻87years, BMI = 29.96 ± 5.53 kg/m²) subjects. OSA diagnosis was from a 2-night home sleep test (ARESTM). Subjective sleep quality, sleep-related quality of life (QOL, Functional Outcomes of Sleep Questionnaire), excessive daytime sleepiness (Epworth Sleepiness Scale), sleep duration and sleep onset and maintenance complaints were assessed. Results: Poor sleep quality and complaints were reported by 19⁻70% of subjects and average sleep duration was 6.4 h. 74.8% of subjects had OSA. OSA diagnosis/severity was not associated with any sleep-related outcomes. Sleep duration was lower in subjects with all conditions (p < 0.05) except OSA. CRS was a significant risk factor for poor sleep-related QOL, sleepiness, sleep quality and insomnia; PTSD for poor sleep-related QOL and insomnia; GERD for poor sleep quality. These associations remained significant after adjustment for, age, BMI, gender, sleep duration and other comorbidities. Conclusions: Sleep complaints are common and related to several health conditions seen in WTC responders. Initial interventions in symptomatic patients with both OSA and comorbid conditions may need to be directed at sleep duration, insomnia or the comorbid condition itself, in combination with intervention for OSA.