A dense ring of the trans-Neptunian object Quaoar outside its Roche limit.

Planetary rings are observed not only around giant planets1, but also around small bodies such as the Centaur Chariklo2 and the dwarf planet Haumea3. Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius4 of 555 km and possesses a roughly 80-km satellite5 (Weywot) that orbits at 24 Quaoar radii6,7. The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar's classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments8, can maintain a ring far away from the body. Moreover, Quaoar's ring orbits close to the 1/3 spin-orbit resonance9 with Quaoar, a property shared by Chariklo's2,10,11 and Haumea's3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies.

Enhancements in laser-generated hot-electron production via focusing cone targets at short pulse and high contrast.

We report on the increase in the accelerated electron number and energy using compound parabolic concentrator (CPC) targets from a short-pulse (∼150 fs), high-intensity (>10^{18} W/cm^{2}), and high-contrast (∼10^{8}) laser-solid interaction. We report on experimental measurements using CPC targets where the hot-electron temperature is enhanced up to ∼9 times when compared to planar targets. The temperature measured from the CPC target is 〈T_{e}〉=4.4±1.3 MeV. Using hydrodynamic and particle in cell simulations, we identify the primary source of this temperature enhancement is the intensity increase caused by the CPC geometry that focuses the laser, reducing the focal spot and therefore increasing the intensity of the laser-solid interaction, which is also consistent with analytic expectations for the geometrical focusing.

Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma.

Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to current medical and surgical therapies, whose tumor cells characteristically show a high level of aneuploidy and genomic instability. We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is a kinase of the spindle assembly checkpoint that controls cell division and cell fate. CFI-402257 is a novel, selective inhibitor of Mps-1 with antineoplastic activity. We found that CFI-402257 suppresses MM growth. We found that Mps-1 is overexpressed in MM and that its expression correlates with poor patients' outcome. In vitro, CFI-402257-mediated inhibition of Mps-1 resulted in abrogation of the mitotic checkpoint, premature progression through mitosis, marked aneuploidy and mitotic catastrophe. In vivo, CFI-402257 reduced MM growth in an orthotopic, syngeneic model, when used as a single agent, and more so when used in combination with cisplatin+pemetrexed, the current standard of care. Our preclinical findings indicate that CFI-402257 is a promising novel therapeutic agent to improve the efficacy of the current chemotherapeutic regimens for MM patients.

Association between menthol-flavoured cigarette smoking and flavoured little cigar and cigarillo use among African-American, Hispanic, and white young and middle-aged adult smokers.

OBJECTIVES: Flavour additives in cigarettes and little cigars and cigarillos (LCCs), which influence smokers' risk perceptions, may reinforce dual flavoured tobacco use. We examined the association among mentholated cigarette use, risk perceptions for flavour additives in LCCs and flavoured LCC smoking behaviour. METHODS: Data from a national probability sample of 964 young and middle-aged adult current cigarette smokers were analysed. Multinomial logistic regression models examined the relationship among mentholated cigarette smoking, risk perceptions and current flavoured LCC use for the analytic sample and gender and race/ethnicity. RESULTS: Daily menthol cigarette smokers, compared to occasional, non-menthol smokers, had increased odds of flavoured LCC smoking (OR=1.75, 95% CI 1.02 to 2.98). This relationship was found for males, blacks/African-Americans and Hispanics/Latinos (p<0.05). Positive perceptions of menthol-flavoured additives in LCCs was associated with increased odds of flavoured LCC use among the analytic sample, males and blacks/African-Americans (p<0.05). Positive perceptions for clove-flavoured, spice-flavoured and alcohol-flavoured additives were also associated with flavoured LCC use among the analytic sample (p<0.05). CONCLUSIONS: Use of menthol-flavoured cigarettes and positive perceptions about menthol-flavoured and other flavour additives in LCCs may contribute to dual use with flavoured LCCs among adult cigarette smokers, specifically those from vulnerable populations.

Aspirin delays mesothelioma growth by inhibiting HMGB1-mediated tumor progression.

High-mobility group box 1 (HMGB1) is an inflammatory molecule that has a critical role in the initiation and progression of malignant mesothelioma (MM). Aspirin (acetylsalicylic acid, ASA) is the most widely used nonsteroidal anti-inflammatory drug that reduces the incidence, metastatic potential and mortality of many inflammation-induced cancers. We hypothesized that ASA may exert anticancer properties in MM by abrogating the carcinogenic effects of HMGB1. Using HMGB1-secreting and -non-secreting human MM cell lines, we determined whether aspirin inhibited the hallmarks of HMGB1-induced MM cell growth in vitro and in vivo. Our data demonstrated that ASA and its metabolite, salicylic acid (SA), inhibit motility, migration, invasion and anchorage-independent colony formation of MM cells via a novel HMGB1-mediated mechanism. ASA/SA, at serum concentrations comparable to those achieved in humans taking therapeutic doses of aspirin, and BoxA, a specific inhibitor of HMGB1, markedly reduced MM growth in xenograft mice and significantly improved survival of treated animals. The effects of ASA and BoxA were cyclooxygenase-2 independent and were not additive, consistent with both acting via inhibition of HMGB1 activity. Our findings provide a rationale for the well documented, yet poorly understood antitumorigenic activity of aspirin, which we show proceeds via HMGB1 inhibition. Moreover, the use of BoxA appears to allow a more efficient HMGB1 targeting while eluding the known gastrointestinal side effects of ASA. Our findings are directly relevant to MM. Given the emerging importance of HMGB1 and its tumor-promoting functions in many cancer types, and of aspirin in cancer prevention and therapy, our investigation is poised to provide broadly applicable information.

Coenzyme Q10, carotenoid, tocopherol, and retinol levels in cord plasma from multiethnic subjects in Hawaii.

Coenzyme Q10 (Q10), carotenoids, tocopherols, and retinol are the major circulating lipid-phase micronutrients (LPM) known to help mitigate oxidative damage and prevent chronic diseases. However, the functions of these compounds in newborns are little understood. This is due, in part, to the paucity of studies reporting their concentrations in this population. We measured Q10, carotenoids, tocopherols, and retinol in cord plasma from 100 multiethnic subjects living in Hawaii using HPLC with diode array and electrochemical detection. Appropriate internal standards were used including, for the first time, custom designed oxidized (UN10) and reduced (UL10) Q10 analogues. These compounds reflected the oxidation of UL10 to UN10 that occurred during sample processing and analysis and thus permitted accurate adjustments of natively circulating Q10 levels. All LPM measured were much lower in cord than in peripheral plasma. Cord plasma levels of total carotenoids, tocopherols, and retinol were approximately 10-fold, 3- to 5-fold and 1.5- to 3-fold lower than those in children or women. Cord plasma levels of total Q10 (TQ10; median, 113 ng/mL) were approximately 2-fold or 7- to 9-fold lower than peripheral plasma levels of neonates or children and adults, respectively. In contrast, the UN10/TQ10 ratio was substantially higher in cord (24%) than in peripheral plasma of children (3-4%) or adults (9%). Among the 5 ethnic groups in our cohort, no differences were observed in the levels of UN10, UL10, or TQ10. However, significant differences in many of the LPM were observed between ethnicities. More research is needed to explain these phenomena.

[Clinical effects of treatment with phytoestrogens in postmenopausal women]. / Effetti clinici del trattamento con fitoestrogeni in donne in post-menopausa.

AIM AND METHODS: Phytoestrogens are plant substances that have estrogenic properties; they haven't steroid structure but they are heterocyclic phenols and for this reason are similar to 17 ß estradiol from the functional and structural point of view; they compete for the same receptor sites of endogenous estrogens, but with an activating capacity a thousand times lower. For this reason, the isoflavones are an alternative to hormone-replacement treatment: they are prescribed to all those women who cannot be treated with HRT for several contraindications, such as thrombosis or breast tumor familiarity. The aim of our study was to demonstrate the effectiveness of soy isoflavones on menopausal symptoms. RESULTS AND CONCLUSION: In our experience, literature data were confirmed, with a 40% reduction of the vasomotor symptoms after 6 months of treatment. Associated with this improvement, there is also the reduction in the degree of insomnia and depressive symptoms. The musculoskeletal pains, however, are not reduced significantly as no positive change was found on vaginal dryness, a major cause of dyspareunia in postmenopausal period.

[Polycystic ovarian syndrome incidence in young women with non-alcoholic fatty liver disease]. / Incidenza di sindrome dell'ovaio policistico in giovani donne affette da steatosi epatica non alcolica.

AIM: Recently, numerous studies have shown significant correlation between hyperandrogenism and elevated insulin levels in many patients with polycystic ovarian syndrome (PCOS). Insuline-Resistance (IR) results in increased circulating levels of this hormone and it is the basis of the metabolic syndrome, characterized by the presence of fatty liver disease (NAFLD), which is pathologically characterized by the accumulation of triglycerides as macro or micro vesicles, in more than 5% of hepatocytes. The aim of our study was to evaluate the incidence of NAFLD in young women with PCOS, who were lean, overweight or obese. METHODS: Particularly, the levels of glucose and insulin, the lipidic profile, and all liver function indices were evaluated; the severity and degree of steatosis were established on the basis of parenchymal echogenicity and the view of intrahepatic venous circulation. RESULTS: Our study showed that NAFLD is a common disease in women with polycystic ovaries, especially with high BMI, but an incidence rate of 40% in lean women too was found. Because steatohepatitis is a risk factor for the developmente of cirrhosis and hepatocellular carcinoma, it is therefore prudent to carry out an ultrasound evaluation of liver in all young patients suffering from polycystic ovary syndrome, regardless of their BMI and the results of serological evaluation of liver. CONCLUSION: This collateral diagnosis that accompanies the diagnosis of Polycystic Ovary Syndrome seems important since this type of patients could be treated with metformin or with thiazoles to reduce insulin-resistance and steatosis as well.

Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial.

BACKGROUND: Polycystic ovary syndrome is the most common cause of chronic anovulation infertility in women in fertile period, and it's characterized by an increased production of androgens and estrogens. The administration of myo-inositol, a B complex vitamin, was associated with a decreased of serum testosterone and simultaneously, due to its ability to increase insulin sensitivity, women who received myo-inositol showed a great improvement of the ovulary function. Besides, the supplementation of inositol improves the oocytes' quality and increase the number of oocytes collected after ovarian stimulation in patients undergoing IVF (in vitro fertilization). AIM: The aim of this study is to determine the effects of myo-inositol on oocyte's quality on a sample of women with polycystic ovary syndrome. MATERIAL AND METHODS: The patients were divided into two groups: patients of Group A in-took 2 g of myo-inositol + 200 microg of folic acid (Inofolic, LO.LI. Pharma, Rome, Italy) while Group B only 200 microg of folic acid, both groups took the treatment twice a day, continuously for 3 months. RESULTS: At the end of treatment, the number of follicles of diameter > 15 mm, visible at ultrasound during stimulation, and the number of oocytes recovered at the time of pick-ups were found to be significantly greater in the group treated with myo-inositol, so as the aver-age number of embryos transferred and embryo Score S1. Significantly reduced was the average number of immature oocytes (vesicles germ and degenerated oocytes) too. CONCLUSIONS: These data suggest that myoinositol may be useful in the treatment of PCOS patients undergoing ovulation induction, both for its insulin-sensitizing activity, and its role in oocyte maturation.

[Clinical effectiveness of N-oleyl-phosphatidyl-ethanolamine (NOPE) in obesity: our experience]. / Efficacia clinica della n-oleil-fosfatidil-etanolamina (NOPE) nella terapia dell'obesita: nostra esperienza.

Adjustment and maintenance of body weight are the result of many process combination, that affect both the gastrointestinal system and other mechanisms in the central nervous system. Often a diet modification alone is not sufficient to guarantee significant changes in body weight. For this reason, it sometimes necessary to make other interventions, in order to help an individual to adhere to the diet as much as possible and to achieve the objectives established. The N-oleyl-phosphatidyl-ethanolamine (NOPE) is a phospholipid. It can be endogenous or exogenous, and it is present in cell membranes and in much of the food. Food intake increases its production; in fact, because of certain stimuli, it is sometimes produced by the epithelial intestine cells too. Another substance whose activity is comparable to NOPE is the epigallocatechin gallate (EGCG), an abundant catechin present in the green tea, which allows a lipid lowering and antioxidant action, and acts on energy consumption as well. The aim of our study was to evaluate the effectiveness of NOPE and EGCG pharmaceutical formulation in a population of obese women, administering the supplement twice daily before meals, for a period of 60 days. The comparison between the effectiveness of the results in a homogeneous group of patients treated with diet and placebo, allows to confirm the data reported in the literature regarding the effectiveness of the pharmaceutical formulation and the absence of side effects.

[Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: our experience with Vitex agnus castus]. / Aspetti psichici del disturbo disforico della fase luteale: nuove prospettive terapeutiche, il vitex agnus castus. Nostra esperienza.

AIM: The premenstrual dysphoric disorder (PMDD) is one of the main problems of the premenstrual phase. It consists of symptoms that sometimes invalidate the scope of employment, social and psycho-affective of patients, requiring thus a diagnostic and therapeutic approach as detailed and accurate as possible. The therapeutic strategies available for this disease are many, but recently the emphasis has been on Vitex agnus castus (VAC), considered by many as evidence drug of choice for both PMS and for the PMDD, being with satisfactory therapeutic properties and small side effects. METHODS AND RESULTS: Our study evaluated a group of patients suffering from PMDD and the clinical efficacy of treatment with VAC (and compared the effectiveness of the results of a more homogeneous group of patients treated with fluoxetine). CONCLUSION: This study confirms the data reported in the literature regarding the effectiveness of VAC therapy with no side effects.

Ethnic differences in weight gain and diabetes risk: the Multiethnic Cohort Study.

AIM: To improve our understanding of excess body weight and risk for diabetes type 2, the study examined the influence of weight change in the Hawaii component, including 78,006 Caucasians, Japanese Americans and Native Hawaiians, of the Multiethnic Cohort Study. METHODS: Participants aged 58.5±9.2 years completed a questionnaire at cohort entry (Qx1), including weight at age 21, and a follow-up questionnaire 5 years later (Qx2). After 14 years of follow-up, 8892 incident diabetes cases were identified through self-reports or linkups with the major health plans in Hawaii. Cox regression analysis was applied, stratified by age and adjusted for confounders, to estimate hazard ratios (HRs). RESULTS: The mean weight gain from age 21 to Qx1 was 10.5±11.0 kg and, between Qx1 and Qx2, 0.8±5.6 kg. Diabetes risk showed a significant dose-response relationship with weight gain from age 21 (P<0.0001). The respective HRs for a weight gain of 5-10 kg and greater or equal to 25 kg were 1.8 (95% CI: 1.7-2.0) and 7.7 (95% CI: 7.1-8.4), while weight loss of greater than 5 kg significantly reduced diabetes risk (HR=0.7; 95% CI: 0.6-0.9). The interaction term of weight change since age 21 with ethnicity was also highly significant (P<0.0001). Compared with stable-weight Caucasians, the adverse effects of weight gain were more pronounced in those of Japanese and Native Hawaiian descent. Weight change between Qx1 and Qx2 conferred a smaller risk. CONCLUSION: These findings support the current public-health recommendations for weight control and particularly among ethnic groups at high risk for diabetes.

[Innovative genetic, clinical and endocrinologic aspects in young females affected by premature ovarian insufficiency]. / Innovativi aspetti genetici, clinici ed endocrini in una giovane popolazione femminile affetta da insufficienza ovarica prematura.

AIM: Heterogeneity premature ovarian insufficiency (POI) is one of the reasons why there are different causes that contribute in determining this type of hormonal disorder. Although the causes have already been established for many types of premature ovarian failure, are still uncertain causes in most cases of idiopathic forms, despite the description of several candidate genes, including BMP-15 gene. The gene under study is precisely the BMP-15, which is part of the superfamily of Transforming Growth Factors-beta or the TGF-ß, which also belong to the growth differentiation factors (GDFs). METHODS: This study examined a sample of Sicilian women suffering from POI, carefully selected according to their age, since in these cases, the genetic factor probably has a greater impact. RESULTS AND CONCLUSION: Identify a mutant gene that causes ovarian failure may be important to make a diagnosis that can predict the possible future development of the disease. The outcome of the studies, however, has not found the gene in question, but it is hypothesized that this may be a direct consequence of the limited amount of women that was done the study, a case which may be rebutted by increasing the number of patients.

[Effects of inositol on oocyte quality in patients affected with polycystic ovary syndrome]. / Effetti dell'inositolo sulla qualità ovocitaria in pazienti affette da sindrome dell'ovaio policistico.

AIM: Polycystic ovary syndrome is the most common cause of chronic anovulation infertility in women in fertile period. The supplementation of inositol, due to its ability to increase insulin sensitivity, improves the oocytes' quality and increase the number of oocytes collected after ovarian stimulation in patients undergoing IVF (In Vitro Fertilization). The aim of our study is to determine the effects of myo-inositol on oocyte's quality on a sample of women with polycystic ovary syndrome. METHODS: The patients were divided into two groups: patients of Group A intook 2 g of myo-inositol + 400 µg of folic acid 2 times a day, continuously for 3 months, while Group B only 400 µg of folic acid. RESULTS AND CONCLUSION: At the end of treatment, the number of follicles of diameter >15 mm, visible at ultrasound during stimulation, and the number of oocytes recovered at the time of pick-ups were found to be significantly greater in the group treated with myo-inositol, so as the average number of embryos transferred and embryo Grade G1. Significantly reduced was the average number of immature oocytes (vesicles germ and degenerated oocytes) too.

[Resistance surveillance of Neisseria gonorrhoeae in a hospital in Santa Fe province, Argentina: 1997-2004]. / Vigilancia de la resistencia de Neisseria gonorrhoeae en un hospital de la provincia de Santa Fe, Argentina: 1997-2004.

Resistance phenotypes characterized by minimum inhibitory concentration, disk diffusion and beta-lactamase production were determined in 434 isolates from patients attending the Sexually Transmitted Disease Service at Dr. José Maria Cullen Hospital in Santa Fe, Argentina. Susceptibility tests to penicillin, tetracycline, ciprofloxacin, espectinomycin, azithromycin and ceftriaxone were performed. Pulsed-field gel electrophoresis was conducted made to on three ciprofloxacin-resistant isolates. Epidemiologically speaking, three interesting events should be highlighted: during 1997, plasmid-mediated high level tetracycline-resistant strains were observed (33.3%); from 2002 to 2004 a significant increase of plasmid-mediated penicillin-resistant strains was registered (9.7% to 34.8%); and in the year 2000 the first two quinolone-resistant strains emerged in the province. In our hospital, the first azithromycin-resistant isolate emerged in 2004. We therefore emphasize the importance of the Clinical Microbiology Laboratory in order to provide information for the empiric treatment of this infection.

Vigilancia de la resistencia de Neisseria gonorrhoeae en un hospital de la provincia de Santa Fe, Argentina: 1997-2004 / Resistance surveillance of Neisseria gonorrhoeae in a hospital in Santa Fe province, Argentina: 1997-2004

Se determinaron los fenotipos de resistencia caracterizados por la concentración inhibitoria mínima, la difusión con discos y la producción de β-lactamasa de 434 aislamientos de Neisseria gonorrhoeae obtenidos de pacientes atendidos en el Servicio de Enfermedades de Transmisión Sexual del Hospital Dr. José María Cullen, Santa Fe, Argentina. Se realizaron pruebas de sensibilidad a los siguientes antimicrobianos: penicilina, tetraciclina, ciprofloxacina, espectinomicina, azitromicina y ceftriaxona. A tres aislamientos resistentes a ciprofloxacina se les realizó electroforesis de campo pulsado. Se destacaron tres situaciones epidemiológicas de interés: en el año 1997, alta incidencia de aislamientos con resistencia plasmídica a tetraciclina (33,3%); en el período 2002-2004, un aumento significativo de la resistencia plasmídica a penicilina (9,7% a 34,8%); y en el año 2000, la emergencia de dos de los tres primeros aislamientos con resistencia a quinolonas del país. El primer aislamiento resistente a azitromicina en nuestro hospital emerge en el 2004. Este trabajo jerarquiza el rol del Laboratorio de Microbiología Clínica en la orientación del tratamiento empírico de la gonorrea.

Resistance phenotypes characterized by minimum inhibitory concentration, disk diffusion and β-lactamase production were determined in 434 isolates from patients attending the Sexually Transmitted Disease Service at Dr. José María Cullen Hospital in Santa Fe, Argentina. Susceptibility tests to penicillin, tetracycline, ciprofloxacin, espectinomycin, azithromycin and ceftriaxone were performed. Pulsed-field gel electrophoresis was conducted made to on three ciprofloxacin-resistant isolates. Epidemiologically speaking, three interesting events should be highlighted: during 1997, plasmid-mediated high level tetracycline-resistant strains were observed (33.3%); from 2002 to 2004 a significant increase of plasmid-mediated penicillin-resistant strains was registered (9.7% to 34.8%); and in the year 2000 the first two quinolone-resistant strains emerged in the province. In our hospital, the first azithromycin-resistant isolate emerged in 2004. We therefore emphasize the importance of the Clinical Microbiology Laboratory in order to provide information for the empiric treatment of this infection.