108 research outputs found

    Eating and aging: Trends in dietary intake among older Americans from 1977–2010

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    We examined trends from 1977–2010 in calorie, macronutrient, and food group intake among US adults 55 and older

    Where people shop is not associated with the nutrient quality of packaged foods for any racial-ethnic group in the United States

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    Background: In the literature, it has been suggested that there are race-ethnic disparities in what Americans eat. In addition, some studies have shown that residents of African American and low-income neighborhoods have less access to grocery stores and supermarkets, which tend to stock healthier foods. However, it is unclear whether differences in food shopping patterns contribute to the poorer nutrient profile of food purchases made by racial-ethnic minorities

    Sphingosine-1 phosphate induces cAMP/PKA-independent phosphorylation of the cAMP response element-binding protein (CREB) in granulosa cells

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    Background and aims: Sphingosine-1 phosphate (S1P) is a lysosphingolipid present in the ovarian follicular fluid. The role of the lysosphingolipid in gonads of the female is widely unclear. At nanomolar concentrations, S1P binds and activates five specific G protein-coupled receptors (GPCRs), known as S1P1-5, modulating different signaling pathways. S1P1 and S1P3 are highly expressed in human primary granulosa lutein cells (hGLC), as well as in the immortalized human primary granulosa cell line hGL5. In this study, we evaluated the signaling cascade activated by S1P and its synthetic analogues in hGLC and hGL5 cells, exploring the biological relevance of S1PR-stimulation in this context. METHODS AND RESULTS. hGLC and hGL5 cells were treated with a fixed dose (0.1 \u3bcM) of S1P, or by S1P1- and S1P3-specific agonists SEW2871 and CYM5541. In granulosa cells, S1P and, at a lesser extent, SEW2871 and CYM5541, potently induced CREB phosphorylation. No cAMP production was detected and pCREB activation occurred even in the presence of the PKA inhibitor H-89. Moreover, S1P-dependent CREB phosphorylation was dampened by the mitogen-activate protein kinase (MEK) inhibitor U0126 and by the L-type Ca2+ channel blocker verapamil. The complete inhibition of CREB phosphorylation occurred by blocking either S1P2 or S1P3 with the specific receptor antagonists JTE-013 and TY52156, or under PLC/PI3K depletion. S1P-dependent CREB phosphorylation induced FOXO1 and the EGF-like epiregulin-encoding gene (EREG), confirming the exclusive role of gonadotropins and interleukins in this process, but did not affect steroidogenesis. However, S1P or agonists did not modulate granulosa cell viability and proliferation in our conditions. Conclusions: This study demonstrates for the first time that S1P may induce a cAMP-independent activation of pCREB in granulosa cells, although this is not sufficient to induce intracellular steroidogenic signals and progesterone synthesis. S1P-induced FOXO1 and EREG gene expression suggests that the activation of S1P\u2013S1PR axis may cooperate with gonadotropins in modulating follicle development

    Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

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    Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

    Waardenburg Syndrome: Clinical Differentiation Between Types I and II

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    Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS. ß 2003 Wiley-Liss, Inc. KEY WORDS: Waardenburg syndrome; genetic heterogeneity; discriminant analysis INTRODUCTION The Waardenburg syndrome (WS), first comprehensively described in 1951, is a genetically heterogeneous condition, each of its forms having a wide clinical spectrum with a very high degree of phenotypic expressivity. In the present paper, we will consider only the two most frequent variants (WSI and WSII) out of the four described so far. These two forms, together accounting for a prevalence of 2 to 3 affected individuals/100,000 in the general population, are determined by non-allelic autosomal dominant mutant genes with a high penetrance. WS is characterized clinically by the association of craniofacial dysmorphim, pigmentation defects, and severe sensorineural congenital hearing impairment. The craniofacial dysmorphisms most commonly seen in affected individuals include telecanthus (in WSI only), broad and high nasal root, hypoplasia of the alae nasi, lower lacrimal dystopia, and synophrys. Telecanthus (dystopia canthorum lateroversa) is classically described as an increase of inner ocular intercantal distance (IID) with preservation of both interpupillary (IPD) and outer intercantal (OID) distances. WS patients with this sign, however, commonly present larger values of the other two measurements, so that they exhibit a certain degree of hypertelorism. Patients frequently display conspicuous pigmentary defects of the irides (totally or partially heterochromic and bright hypochromic blue irides), hypopigmented skin spots, and partial hair albinism (white forelock or early graying). The first variant (WSI), with telecanthus, is caused by mutations at the PAX3 gene located in 2q35, while the second (WSII) is determined by other non-allelic autosomal dominant mutations located in the region 3p12.3 ! 3p14.1 of the MITF gene. Many of these are point mutations involving single-base substitutions and the number of different mutations described so far for both loci is so large that the molecular screening for them in WS can not be routinely performed in most laboratories. Because of all this, the differential diagnosis between variants I and II still relies largely on classic clinical methods. Clinical signs and symptoms are similar in both conditions, but telecanthus is known to occur only in WSI; the other characteristics have contrasting frequencies in both forms, especially iris and hair pigmentary disturbances and deafness. The penetrance of the last trait is higher in the second variant of WS, which has therefore a poorer clinical prognosis. Telecanthus (sometimes hypertelorism) is the most important sign for the differentiation between both forms, because it is present in the vast majority (95-99%) of WSI patients and virtually absent in those with the WSII variant. The presence of conspicuous craniofacial dysmorphisms in WS explains why the condition has been widely studied anthropometrically. The first of these studies was performed on Waardenburg's original data by Since the penetrance of the telecanthus trait and consequently the efficiency of the W index-although generally high-are both incomplete In this paper, we describe 59 individuals affected by the Waardenburg syndromes WSI and WSII, belonging to 25 Brazilian families. A detailed craniofacial phenotypic description of all affected individuals is presented, as well as the values of several measurements taken in these patients. The relative frequencies of cardinal signs and the values of craniofacial measurements are used to compare, through discriminant analysis, WSI and WSII affected individuals. MATERIALS AND METHODS Out of the 25 families studied personally, 18 were ascertained in the Laboratory of Human Genetics (LGH, Departamento de Biologia, IB USP, São Paulo) and seven were examined at the Hospital de Reabilitação de Anomalias Cranio-Faciais (HRAC, Faculdade de Odontologia, USP, Bauru). For this, we used a standardized routine for physical examination that included the investigation, in all affected individuals (with the exception of a few instances in which one measurement could not be recorded and the corresponding feature could not be evaluated objectively), of the following eight cardinal signs and symptoms of WS: telecanthus, synophrys, iris pigmentation disturbances, localized albinism on hair (white forelock and early graying), hearing impairment, nasal root hyperplasia, hypopigmented skin spots, and lower lacrimal dystopia. We selected also, through review of the international literature, 44 different papers published from 1951 to 1995 with complete clinical presentation of cases of WS Waardenburg Syndrome 225 non-mentioned characteristic was absent, the estimate for its frequency is given by under the hypothesis (b) that the non-mentioned sign/ symptom was not investigated, its frequency estimate is given by x 00 ¼ X/(X þ Y) ¼ X/(N À Z), with expected binomial variance var(x 00 ) ¼ x 00 (1 À x 00 )/(N À Z). Obviously, the true estimate of the frequency is given by an unknown quantity within an interval with lower und upper limits given by x 0 and x 00 . If there is no additional information enabling us to choose one out of the two hypotheses above, an estimate of the true frequency x can be obtained by weighing the estimates x 0 and x 00 by the reciprocal of their expected binomial variances. This estimate will be used throughout this work to contrast the frequencies of the cardinal signs in a sample of WSI and WSII patients combining our data with those from the literature. We also determined-in random samples of Caucasian individuals stratified by sex and age (total of 300 individuals) and in affected individuals and in their relatives belonging to ten of our 25 families-23 different craniofacial measurements of interest in the diagnosis of WS. Some of these measurements were used for comparing controls and patients as well as types I and II of WS. 226 Pardono et al. We have classified as WSI all the patients, familial or isolated, that presented conspicuous telecanthus. In order to classify as WSI a case of WS without telecanthus, this affected individual should always belong to a family with at least one typical case of WSI (with telecanthus). Therefore, all cases of WSI without telecanthus presented here are familial, whereas all isolated cases of WS classified as WSI present with the sign. Inversely, all cases of WS classified as WSII are necessarily familial, that is, they belong strictly to families with at least one more affected individual, none of them presenting telecanthus. In the cases selected from literature, we applied the same classification criteria, systematically disregarding the classification of isolated cases of WS without telecanthus as being WSII. In the presentation of our cases in the Results and Discussion section, all isolated WS patients without telecanthus were grouped in a group labelled as WSII?, but their data were not used in the statistical analyses described below. For the study of cardinal characteristics, the application of the above-mentioned stringent criteria to the cases from literature enabled us to consider a total of 461 WSI patients (29 of them not presenting telecanthus) and 121 carriers of the WSII variant. With the addition of our own data to those from the literature, the discriminant analysis performed with categorical data was based, therefore, on totals of 491 WSI and 142 WSII patients, respectively. The techniques of statistical analysis used throughout this paper are detailed in standard textbooks (e.g., Zar [1999]). Those on linear and non-linear discriminant analysis in particular are detailed in Smith [1947, 1969], Penrose [1947], and Karn and Penrose [1951]. RESULTS AND DISCUSSION Description of Cases Using a modification of the genealogy symbols proposed by Discriminant Analysis Using the Frequencies of Cardinal Signs and Symptoms The estimated frequencies of the eight cardinal characteristics of WS were calculated from reliable case descriptions in the literature and are shown in Waardenburg Syndrome 227 Comparing the observed frequencies of each sign in the groups of WSI and WSII patients through chisquared tests in 2 Â 2 contingency tables, we obtained in all cases test figures that were significant at least at the 1% level. The elements necessary for performing a simplified categoric discriminant analysis, together with an application example, are summarized in Since there are only seven other possible signs besides telecanthus, all the possible combinations of these seven signs/symptoms (presence or absence) reduce to 2 7 ¼ 128. 38 out of these 128 combinations generate probability figures larger than 95% or less than 5% favoring the diagnosis of WSI and are shown in We could obtain, combining our data with those from the literature, complete individual phenotypic descriptions of 111 patients affected by WSII out of the 142 used for deriving the probabilities shown in Discriminant Analysis Based on Craniofacial Measurements First we compared the craniofacial measurements between WSI and WSII patients, and between WS patients and controls through t tests with allowance for variance heterogeneity. Using as selection criterion all variables that were statistically different between any of the two comparison groups at least at the 0.001 significance level, we chose the following variables to be used on discriminant analysis: inner intercanthal distance (IID); outer intercanthal distance (OID); interpupillary distance (IPD); lower interlacrimal distance (LID); nose interalar distance (IAD); mean length of ear (EML), obtained by averaging the longitudinal length of both auricles; and the W index (WI), a composite measure used in the literature for separating WSI and WSII patients and described in the introduction section. We decided to also include the variables facial length or morphological face height (MFH) and the mean width of ear (EMW), a measurement obtained by averaging the transversal length of both auricles. These two measurements, in spite of not showing statistical significance at the 0.001 level, exhibited differences at a critical level much less than 0.01. The statistical parameters of these nine measurements, estimated in the groups of WSI and WSII patients and controls, are shown i

    Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study

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    Purpose: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. Methods: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January\u2013February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. Results: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). Conclusions: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management
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