The genome-wide distribution of linkage disequilibrium (LD) determines the strategy for selecting markers for association studies, but it varies between populations. We assayed LD in large samples ...(200 individuals) from each of 11 well-described population isolates and an outbred European-derived sample, using SNP markers spaced across chromosome 22. Most isolates show substantially higher levels of LD than the outbred sample and many fewer regions of very low LD (termed 'holes'). Young isolates known to have had relatively few founders show particularly extensive LD with very few holes; these populations offer substantial advantages for genome-wide association mapping.
This article describes the first results obtained from the Surface Waves Investigation and Monitoring (SWIM) instrument carried by the China France Oceanography Satellite (CFOSAT), which was launched ...on October 29, 2018. SWIM is a Ku-band radar with a near-nadir scanning beam geometry. It was designed to measure the spectral properties of surface ocean waves. First, the good behavior of the instrument is illustrated. It is then shown that the nadir products (significant wave height, normalized radar cross section, and wind speed) exhibit an accuracy similar to standard altimeter missions, thanks to a new retracking algorithm, which compensates a lower sampling rate compared to standard altimetry missions. The off-nadir beam observations are analyzed in detail. The normalized radar cross section varies with incidence and wind speed as expected from previous studies presented in the literature. We illustrate that, in order to retrieve the wave spectra from the radar backscattering fluctuations, it is crucial to apply a speckle correction derived from the observations. Directional spectra of ocean waves and their mean parameters are then compared to wave model data at the global scale and to in situ data from a selection of case studies. The good efficiency of SWIM to provide the spectral properties of ocean waves in the wavelength range 70-500 m is illustrated. The main limitations are discussed, and the perspectives to improve the data quality are presented.
Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of ...proinflammatory cytokines, such as interleukin 6, tumor necrosis factor alpha, and interferon gamma, have been proposed as mediators of cancer cachexia; these data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. We therefore studied the relationship between serum leptin and serum cytokines interleukin 6 and tumor necrosis factor alpha levels in advanced-stage cancer patients. Twenty-nine advanced stage cancer patients (all but one stage IV) with tumors at various sites were included in the study. A direct correlation between body mass index and serum leptin levels was found both in cancer patients and in healthy individuals. The serum levels of interleukin 6 were significantly higher in cancer patients than in healthy individuals. In cancer patients an inverse correlation was found between serum levels of leptin and proinflammatory cytokines. There was an inverse correlation between the Eastern Cooperative Oncology Group performance status scale and serum levels of leptin. Regarding survival, patients with very high serum levels of proinflammatory cytokines and very low levels of leptin had very short survival. Although obtained in a cancer patient population not overtly cachectic, our results provide further evidence that a simple dysregulation of leptin production and/or release cannot be involved in cancer-associated pathophysiological changes leading to cachexia.
Obstructive Sleep Apnea (OSA) represents an emerging public health concern with great impact on cardiovascular state. Oxidative stress (OS), inflammation and altered Nitric Oxide (NO) production are ...recognized as prominent mechanisms of many acute and chronic diseases and even of the normal aging process. They are investigated as major pathophysiological processes in OSA through the analysis and comparison of significative and validated biomarkers.
The review is developed using as key terms "sleep apnea", "oxidative stress", "inflammation", and "endothelial dysfunction". Included studies must have followed the American Academy of Sleep Medicine guidelines according to the diagnosis and classification of OSA. Lipid, protein and DNA oxidation products, PCR, IL-6, IL-8, TNF-α, NO and nitrosative stress compounds, and endothelial functioning tests have been detected for their contribution in OSA along the last 3 decades.
Nocturnal intermittent hypoxia has emerged to be significantly associated to oxidative/nitrosative stress, increase in pro-inflammatory markers, imbalance in NO production, and endothelium impairment. Body Mass Index (BMI) contribution needs further clarifications. Continuous Positive Airway Pressure (CPAP) therapy has demonstrated beneficial effects on vascular function and pro-inflammatory milieu in OSA.
Oxidative stress and Inflammation significantly correlate with OSA; similarly, vascular functioning is impaired in accordance to unregulated levels of NO and derived compounds. Continuous Positive Airway Pressure markedly improves oxidative stress, inflammation and endothelial dysfunction in OSA.
To evaluate the incidence and dose-dependency of mitoxantrone (MTX)-associated acute myelocytic leukemia (AML) in the network of Italian multiple sclerosis (MS) clinics.
We performed a multicenter ...retrospective cohort study of patients treated with MTX in MS centers under the Italian national health care system between 1998 and 2008. Demographic, disease, treatment, and follow-up information were collected using hospital records.
Data were available for 3,220 patients (63% women) from 40 Italian centers. Follow-up (mean ± SD) was 49 ± 29 months (range 12-140 months). We observed 30 cases of AML (incidence 0.93% 95% confidence interval 0.60%-1.26%). The mean cumulative dose was higher in patients with AML (78 vs 65 mg/m(2), p = 0.028). The median interval from the start of therapy to AML diagnosis was longer than expected at 33 months (range 13-84 months); 8 patients (27%) developed AML 4 years or more after the first MTX infusion. The rate of mortality associated with AML was 37%.
This higher than expected risk of AML and related mortality requires that treatment decisions must be made jointly between clinicians and patients who understand their prognosis, treatment options, and treatment-related risks. The now large exposed MS population must be monitored for hematologic abnormalities for at least 6 years from the end of therapy, to ensure the rapid actions needed for early diagnosis and treatment of AML.
Background: Pegylated interferon (PEG-IFN)- alpha monotherapy is the current standard of care for short-term antiviral treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). ...We aimed to assess the safety and efficacy of PEG-IFN- alpha plus adefovir dipivoxil (ADV) versus PEG-IFN- alpha monotherapy for compensated HBeAg-negative CHB. Methods: Amulticentre randomized controlled trial was performed in eight outpatient hepatology/infectious disease clinics in central Italy. A total of 60 patients (67% male and median age 48 years) with biopsy-proven HBeAg-negative compensated CHB (mean alanine aminotranferase ALT levels 3.3 plus or minus 3x the upper normal limit and serum hepatitis B virus HBV DMA 5.8 plus or minus 0.9 log sub(10) IU/ml) were randomized at baseline to receive PEG-IFN- alpha 2a 180 mu g/week plus ADV 10 mg/day or PEG-lFN- alpha 2a monotherapy for 48 weeks. Post-treatment follow-up was for 24 additional weeks. The primary end point was sustained HBV DNA suppression defined as serum HBV DNA<2,000 IU/ml after 24 weeks of post-treatment follow-up. The secondary end point was ALT normalization at the end of follow-up. Results: At week 48, HBV DNA was undetectable in 20/30 (67%) in the combination group versus 11/30 (37%) patients in the monotherapy group (P=0.02). ALT normalization was achieved in 17/30 (57%) versus 10/30 (30%) patients, respectively (P=0.03). At week 72, sustained virological response was achieved in 7/30 (23.3%) in the combination group versus 6/30 (20%) patients in the monotherapy group (P=0.75); 5 (16%) patients in each group dropped out because of adverse events or non-compliance. Conclusions: In HBeAg-negative CHB, combination PEG-IFN- alpha 2a plus ADV for 48 weeks is safe and resulted in greater on-treatment efficacy than PEG-IFN- alpha 2a monotherapy. No difference in sustained virological and biochemical response rates were observed between the two treatment regimens.
Thiazide diuretics have been recommended as a first-line antihypertensive treatment, although the choice of 'the right drug in the individual essential hypertensive patient' remains still empirical. ...Essential hypertension is a complex, polygenic disease derived from the interaction of patient's genetic background with the environment. Pharmacogenomics could be a useful tool to pinpoint gene variants involved in antihypertensive drug response, thus optimizing therapeutic advantages and minimizing side effects.
We looked for variants associated with blood pressure response to hydrochlorothiazide over an 8-week follow-up by means of a genome-wide association analysis in two Italian cohorts of never-treated essential hypertensive patients: 343 samples from Sardinia and 142 from Milan. TET2 and CSMD1 as plausible candidate genes to affect SBP response to hydrochlorothiazide were identified. The specificity of our findings for hydrochlorothiazide was confirmed in an independent cohort of essential hypertensive patients treated with losartan. Our best findings were also tested for replication in four independent hypertensive samples of European Ancestry, such as GENetics of drug RESponsiveness in essential hypertension, Genetic Epidemiology of Responses to Antihypertensives, NORdic DILtiazem intervention, Pharmacogenomics Evaluation of Antihypertensive Responses, and Campania Salute Network-StayOnDiur. We validated a polymorphism in CSMD1 and UGGT2.
This exploratory study reports two plausible loci associated with SBP response to hydrochlorothiazide: TET2, an aldosterone-responsive mediator of αENaC gene transcription; and CSMD1, previously described as associated with hypertension in a case-control study.
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