Rotavirus vaccine efficacy in African and Asian countries

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Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air

Background: In the last decade many studies showed that the exhaled breath of subjects suffering from several pathological conditions has a peculiar volatile organic compound (VOC) profile. The objective of the present work was to analyse the VOCs in alveolar air to build a diagnostic tool able to identify the presence of pancreatic ductal adenocarcinoma in patients with histologically confirmed disease. Methods: The concentration of 92 compounds was measured in the end-tidal breath of 65 cases and 102 controls. VOCs were measured with an ion-molecule reaction mass spectrometry. To distinguish between subjects with pancreatic adenocarcinomas and controls, an iterated Least Absolute Shrinkage and Selection Operator multivariate Logistic Regression model was elaborated. Results: The final predictive model, based on 10 VOCs, significantly and independently associated with the outcome had a sensitivity and specificity of 100 and 84% respectively, and an area under the ROC curve of 0.99. For further validation, the model was run on 50 other subjects: 24 cases and 26 controls; 23 patients with histological diagnosis of pancreatic adenocarcinomas and 25 controls were correctly identified by the model. Conclusions: Pancreatic cancer is able to alter the concentration of some molecules in the blood and hence of VOCs in the alveolar air in equilibrium. The detection and statistical rendering of alveolar VOC composition can be useful for the clinical diagnostic approach of pancreatic neoplasms with excellent sensitivity and specificity

Acute cardiovascular changes in women undergoing in vitro fertilisation (IVF), a systematic review and meta-analysis

Objectives: Ovarian stimulation during fertility treatment leads to profound maternal physiological changes. Women undergoing in vitro fertilisation (IVF) may be at an increased risk of future cardiovascular morbidity, though little is known about the effects on maternal cardiovascular function. We aim to systematically review whether IVF treatment is associated with changes in maternal haemodynamic parameters, and the effects of different protocols. Study Design: A systematic review and meta-analysis of English language studies identified on Medline and EMBASE database, between 1978, to 2019. Search terms: IVF, maternal haemodynamics, and cardiovascular. Studies reporting on ovulation induction, intrauterine insemination, and oocyte donation were excluded. Methodological quality was assessed by using the adapted Critical Appraisal Skills Programme (CASP) checklist. A meta-analysis was conducted for blood pressure and heart rate on patients undergoing the long GnRH agonist protocol according to Cochrane guidelines. We considered four time points in the IVF cycle, in chronological order: pre-treatment, pituitary down regulation, peak oestradiol and the luteal phase. Results: Nine suitable studies were identified; four fulfilled the criteria for meta-analysis. Two studies measuring heart rate found a significant increase in heart rate from pituitary down-regulation to peak estradiol levels, which was supported by the meta-analysis (3.78 \ub1 2.18 (p= < 0.0001)). Three studies reported a significant decrease in blood pressure from baseline, with those suitable for meta-analysis showing a significant decrease in mean arterial pressure (-2.08 \ub1 1.79 (p= < 0.0001)). Cardiac functional changes were reported for all studies and the changes depended on the type of protocol used. Conclusions: In Vitro Fertilisation leads to acute changes in maternal haemodynamics at different time points of the stimulation protocol. We found an increase in heart rate from pituitary down-regulation to peak estradiol levels and a significant decrease in blood pressure from baseline or pituitary down-regulation to the luteal phase. Cardiac functional changes were reported for all studies on the agonist protocol, but no significant changes were found using the antagonist protocol. It remains unclear as to whether these acute changes were associated with pregnancy complications or chronic cardiovascular sequelae

Glycemic Control in Type 1 Diabetes Mellitus During COVID-19 Quarantine and the Role of In-Home Physical Activity.

Background: To limit the spread of coronavirus disease 2019 (COVID-19), governments have ordered a series of restrictions that may affect glycemic control in individuals with type 1 diabetes mellitus (T1DM), since physical activity (PA) was not allowed outside home. Methods: We retrospectively evaluated glycemic control of individuals with T1DM using hybrid closed loop (HCL) system in the period before the SARS-CoV-2 outbreak in Italy (February 10-23, 2020-Time 1), when movements were only reduced (February 24-March 8, 2020-Time 2) and during complete lockdown (March 9-22, 2020-Time 3). Information about regular PA (at least 3 h per week) prior and during the quarantine was collected. Results: The study included 13 individuals with a median age of 14.2 years and a good glycemic control at baseline (glucose management indicator of 7%, time in range [TIR] of 68%, time below range [TBR] of 2%). All individuals continued to show good glycemic control throughout the study period. There was an increase in TIR during the study period (+3%) and TIR was significantly higher during Time 3 (72%) than during Time 2 (66%). TBR was significantly lower during Time 3 (1%) both compared with Time 1 and Time 2 (2%). A meaningful variance in TIR at Time 3 between individuals who performed or not PA during quarantine and a significant increase in TIR between Time 2 and Time 3 in individuals both doing PA at baseline and during quarantine was found. At logistic regression, only the presence of PA during quarantine significantly predicted a TIR >70%. Conclusions: Glycemic control of T1DM in adolescents using HCL system did not worsen during the restrictions due to COVID-19 pandemics and further improved in those who continued PA during the quarantine. Maintaining regular PA in a safe home environment is an essential strategy for young individuals with T1DM during the COVID-19 crisis

An Easy and Reliable Strategy for Making Type I Interferon Signature Analysis Comparable among Research Centers

Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of the IFN score is proposed for the screening of monogenic interferonopathies, like the Aicardi-Gouti\ue8res syndrome, or to stratify subjects with systemic lupus erythematosus to receive IFN-targeted treatments. Apart from these scenarios, there is no agreement on the diagnostic value of the score in distinguishing IFN-related disorders from diseases dominated by other types of cytokines. Since the IFN score is currently measured in several research hospitals, merging experiences could help define the potential of scoring IFN inflammation in clinical practice. However, the IFN score calculated at different laboratories may be hardly comparable due to the distinct sets of IFN-stimulated genes assessed and to different controls used for data normalization. We developed a reliable approach to minimize the inter-laboratory variability, thereby providing shared strategies for the IFN signature analysis and allowing different centers to compare data and merge their experiences

Potential role of circulating microRNAs as early markers of preeclampsia

Abstract Objective To identify microRNAs (miRNAs) differentially expressed at early stages of gestation (12–14 weeks) in the serum of pregnant women, who later developed severe preeclampsia (sPE) in the third trimester of pregnancy ( n = 24) compared to women with normal pregnancy ( n = 24). Materials and Methods Sera from 12–14-week-gestation whole blood were subjected to microarray analysis with TaqMan Low Density Array chips (human microRNA panel V3.0), and to quantitative real-time polymerase chain reaction. Results By using the TaqMan Low Density Array chip technology, 19 mature miRNAs appeared differentially expressed in the group of women who later developed sPE as compared to normal women. The expression of four miRNAs (miR-1233, miR-520, miR-210, miR-144) was validated by quantitative real-time polymerase chain reaction analysis. MiR-1233 was the most overexpressed in the serum of women who later developed sPE. Conclusion Circulating miRNAs deserve further investigation in order to explore their potential role in the pathogenesis of preeclampsia. In particular, miR-1233 might represent a potential marker of early sPE

Maternal hemodynamics : a method to classify hypertensive disorders of pregnancy

BACKGROUND: The classification of hypertensive disorders of pregnancy is based on the time at the onset of hypertension, proteinuria, and other associated complications. Maternal hemodynamic interrogation in hypertensive disorders of pregnancy considers not only the peripheral blood pressure but also the entire cardiovascular system, and it might help to classify the different clinical phenotypes of this syndrome. OBJECTIVE: This study aimed to examine cardiovascular parameters in a cohort of patients affected by hypertensive disorders of pregnancy according to the clinical phenotypes that prioritize fetoplacental characteristics and not the time at onset of hypertensive disorders of pregnancy. STUDY DESIGN: At the fetal-maternal medicine unit of Ziekenhuis Oost-Limburg (Genk, Belgium), maternal cardiovascular parameters were obtained through impedance cardiography using a noninvasive continuous cardiac output monitor with the patients placed in a standing position. The patients were classified as pregnant women with hypertensive disorders of pregnancy who delivered appropriate- and small-for-gestational-age fetuses. Normotensive pregnant women with an appropriate-for-gestational-age fetus at delivery were enrolled as the control group. The possible impact of obesity (body mass index 6530 kg/m2) on maternal hemodynamics was reassessed in the same groups. RESULTS: Maternal age, parity, body mass index, and blood pressure were not significantly different between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and hypertensive disorders of pregnancy/small-for-gestational-age groups. The mean uterine artery pulsatility index was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group. The cardiac output and cardiac index were significantly lower in the hypertensive disorders of pregnancy/small-for-gestational-age group (cardiac output 6.5 L/min, cardiac index 3.6) than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group (cardiac output 7.6 L/min, cardiac index 3.9) but not between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and control groups (cardiac output 7.6 L/min, cardiac index 4.0). Total vascular resistance was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group and the control group. All women with hypertensive disorders of pregnancy showed signs of central arterial dysfunction. The cardiovascular parameters were not influenced by gestational age at the onset of hypertensive disorders of pregnancy, and no difference was observed between the women with appropriate-for-gestational-age fetuses affected by preeclampsia or by gestational hypertension with appropriate-for-gestational-age fetuses. Women in the obese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and obese/hypertensive disorders of pregnancy/small-for-gestational-age groups showed a significant increase in cardiac output, as well as significant changes in other parameters, compared with the nonobese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and nonobese/hypertensive disorders of pregnancy/small-for-gestational-age groups. CONCLUSION: Significantly low cardiac output and high total vascular resistance characterized the women with hypertensive disorders of pregnancy associated with small for gestational age due to placental insufficiency, independent of the gestational age at the onset of hypertension. The cardiovascular parameters were not significantly different in the women with appropriate-for-gestational-age or small-for-gestational-age fetuses affected by preeclampsia or gestational hypertension. These findings support the view that maternal hemodynamics may be a candidate diagnostic tool to identify hypertensive disorders in pregnancies associated with small-for-gestational-age fetuses. This additional tool matches other reported evidence provided by uterine Doppler velocimetry, low vascular growth factors in the first trimester, and placental pathology. Obesity is associated with a significantly higher cardiac output and outweighs other determinants of hemodynamics in pregnancy; therefore, in future studies on hypertensive disorders, obesity should be studied as an additional disease and not simply as a demographic characteristic

Dysregulated chaperones associated with cell proliferation and negative apoptosis regulation in the uterine leiomyoma

Uterine leiomyomas are benign smooth muscle cell tumors that originate from the myometrium. In this study we focus on dysregulated chaperones associated with cell proliferation and apoptosis. Paired tissue samples of 15 leiomyomas and adjacent myometria were obtained and analyzed by two-dimensional gel electrophoresis (2-DE). Mass spectrometry was used for protein identification and western blotting for 2-DE data validation. The values of 6 chaperones were found to be significantly different in the leiomyoma when compared with the myometrium. A total of 4 proteins were upregulated in the leiomyoma and 2 proteins were downregulated. Calreticulin and 78 kDa glucose-regulated protein were further validated by western blotting because the first is considered a marker of cell proliferation, while the second protects against apoptotic cell death. In addition, we also validated the two downregulated proteins heat shock protein \u3b2-1 and heat shock 70 kDa protein 1A. Our study shows the existence of a dysregulation of chaperone proteins associated with leiomyoma development. Functional studies are needed to ascertain the role of these chaperones in the leiomyoma. This may be crucial for the further development of specific inhibitors against the activity of these proteins in order to block the growth of the leiomyoma

Inflammatory bowel disease and patterns of volatile organic compounds in the exhaled breath of children: A case-control study using Ion Molecule Reaction-Mass Spectrometry

Inflammatory bowel diseases (IBD) profoundly affect quality of life and have been gradually increasing in incidence, prevalence and severity in many areas of the world, and in children in particular. Patients with suspected IBD require careful history and clinical examination, while definitive diagnosis relies on endoscopic and histological findings. The aim of the present study was to investigate whether the alveolar air of pediatric patients with IBD presents a specific volatile organic compounds' (VOCs) pattern when compared to controls. Patients 10-17 years of age, were divided into four groups: Crohn's disease (CD), ulcerative colitis (UC), controls with gastrointestinal symptomatology, and surgical controls with no evidence of gastrointestinal problems. Alveolar breath was analyzed by ion molecule reaction mass spectrometry. Four models were built starting from 81 molecules plus the age of subjects as independent variables, adopting a penalizing LASSO logistic regression approach: 1) IBDs vs. controls, finally based on 18 VOCs plus age (sensitivity = 95%, specificity = 69%, AUC = 0.925); 2) CD vs. UC, finally based on 13 VOCs plus age (sensitivity = 94%, specificity = 76%, AUC = 0.934); 3) IBDs vs. gastroenterological controls, finally based on 15 VOCs plus age (sensitivity = 94%, specificity = 65%, AUC = 0.918); 4) IBDs vs. controls, built starting from the 21 directly or indirectly calibrated molecules only, and finally based on 12 VOCs plus age (sensitivity = 94%, specificity = 71%, AUC = 0.888). The molecules identified by the models were carefully studied in relation to the concerned outcomes. This study, with the creation of models based on VOCs profiles, precise instrumentation and advanced statistical methods, can contribute to the development of new non-invasive, fast and relatively inexpensive diagnostic tools, with high sensitivity and specificity. It also represents a crucial step towards gaining further insights on the etiology of IBD through the analysis of specific molecules which are the expression of the particular metabolism that characterizes these patients

Burden of non-communicable diseases among adolescents aged 10–24 years in the EU, 1990–2019 : a systematic analysis of the Global Burden of Diseases Study 2019

Funding Bill & Melinda Gates FoundationPeer reviewedPublisher PD