The overall goal of The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study is to evaluate the ...roles of repeated enteric infection and poor dietary intakes on the development of malnutrition, poor cognitive development, and diminished immune response. The use of 8 distinct sites for data collection from Latin America, sub-Saharan Africa, and South Asia allow for an examination of these relationships across different environmental contexts. Key to testing study hypotheses is the collection of appropriate data to characterize the dietary intakes and nutritional status of study children from birth through 24 months of age. The focus of the current article is on the collection of data to describe the nature and adequacy of infant feeding, energy and nutrient intakes, and the chosen indicators to capture micronutrient status in children over time.
Although genetics, maternal undernutrition and low birth weight status certainly play a role in child growth, dietary insufficiency and infectious diseases are key risk factors for linear growth ...faltering during early childhood. A primary goal of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study is to identify specific risk factors associated with growth faltering during the first 2 years of life; however, growth in early childhood is challenging to characterize because growth may be inherently nonlinear with age. In this manuscript, we describe some methods for analyzing longitudinal growth to evaluate both short- and long-term associations between risk factors and growth trajectories over the first 2 years of life across 8 resource-limited settings using harmonized protocols. We expect there will be enough variability within and between sites in the prevalence of risk factors and burden of linear growth faltering to allow us to distinguish some of the key pathways to linear growth faltering in the MAL-ED study.
Abstract Background Human herpesvirus-6 (HHV-6) has been associated with a wide spectrum of diseases. (r)-9-4-Hydroxy-2-(hydroxymethyl)butylguanine (H2G) is an acyclic guanosine analogue that is ...structurally similar to acyclovir and is in clinical development for treatment of herpesvirus infections. H2G has been found to have activity against HSV type 1, HSV type 2, and HHV-6 in lymphoblast cell lines. A new anti-viral duplex drug, 3′-azido-3′-deoxythymidylyl-(5′ → 2- O )-3- O -octadecyl- sn -glycerol (AZT–lipid–PFA), linking zidovudine (AZT) and foscarnet (PFA) via a lipophilic octadecylglycerol residue (lipid) also exhibits anti-viral activities against HIV, HSV type 1 and HCMV. Objective To assess the efficacy of H2G and AZT–lipid–PFA conjugate against HHV-6. Study design Drug-associated toxicity and proliferative response were evaluated. We conducted in vitro experiments to determine the efficacy of H2G and an AZT–lipid–PFA conjugate in interfering with expression HHV-6 viral transcript in primary human peripheral blood mononuclear cells (PBMC). Results Both H2G and AZT–lipid–PFA were effective at inhibiting expression of HHV-6 gene transcript at comparable concentrations. Additionally, while AZT–lipid–PFA treatment was toxic to cells at concentrations above 5 μM, H2G treatment was associated with minimal cytotoxicity. Conclusion These data suggest the potential application of these anti-viral compounds in controlling HHV-6 infection.
Klinefelter's syndrome (KS) is the most common sex-chromosome disorder in men, affecting ∼1:660 men, and is a rather common cause of infertility, hypogonadism and learning disability. Traditionally, ...men with KS have been described as tall, slim, narrow shouldered, broad hipped, with hypergonadotrophic hypogonadism and small testes. Recent studies showed an increased risk of diabetes and an unfavourable change in body composition; with accumulation of body fat and decreased muscle mass and a concomitant decrease in insulin sensitivity, muscle strength and oxygen consumption capacity. Here, we review the data on body composition, insulin resistance and metabolic syndrome in relation to testosterone in both KS patients and normal men. Treatment with testosterone in hypogonadal states (other than KS) seems to improve body composition in both clinical and experimental studies. Despite the lack of such studies in KS, we recommend testosterone treatment to KS patients with low serum testosterone or increased LH and change in body composition.
Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating ...efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence‐based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review.
Based on this evidence, families can be provided with evidence‐based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4–6 months of life. If breastfeeding is insufficient or not possible, infants at high‐risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.
Abstract Background Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, ...and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings. Methods The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered. Results Coverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guérin coverage was high across all sites, 87–100%, whereas measles vaccination rates ranged widely, 73–100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific. Conclusions Our findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission.
Abstract
Background
Pain is a serious issue in our aging society. Metamizole is one of the most commonly used analgesics. In addition, metamizole has been shown to attenuate the pharmacodynamics ...response to aspirin as measured by platelet function tests. However, the extent to which this laboratory effect translates to clinical outcome in patients is unknown.
Methods
We conducted a nationwide analysis based on health insurance database including 9.2 million patients in Germany. All patients with a cardiovascular event in 2014 and subsequent secondary prevention with aspirin were followed up for 36 months. Inverse probability of treatment weighting (IPTW) analysis was performed to examine mortality rates between patients on aspirin-metamizole co-medication and aspirin medication alone. Myocardial infarction (MI) and stroke/transient ischemic attack (TIA) events were also documented.
Results
26,200 patients received continuous aspirin medication alone and 5,946 received co-medication with aspirin and metamizole. In the IPTW analysis, significantly increased mortality was observed in the co-medication group (15.6% vs. 24.4%, hazard ratio (HR)=1.66, 95% confidence interval (CI) 1.56–1.76; p<0.0001). MI and stroke/TIA were also increased (MI: 1,370 5.2% vs. 355 5.9%; HR=1.18, 95% CI 1.05–1.32; p=0.0066, relative risk (RR) 1.14, absolute risk increase (ARI) 0.71%, number needed to harm (NNH) 140. Stroke/TIA: 1,901 7.3% vs. 506 8.5%; HR=1.22, 95% CI 1.11–1.35; p<0.0001, RR 1.17, ARI 1.21%, NNH 82).
Conclusion
In this nationwide observational study, aspirin-metamizole co-medication was associated with excess mortality. This was partly due to ischemic events (MI and stroke/TIA), which were also more frequent in the co-medication patients. Therefore, metamizole should be used with caution in aspirin-treated patients for secondary prevention
Funding Acknowledgement
Type of funding sources: None.
3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT ...(5-year follow-up) indicating long-term preventive effect of SIT. We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT. One hundred and forty-seven subjects, aged 16-25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3-year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation. The significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly less actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms odds ratio 2.5 (1.1-5.9). Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper-responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow-up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5-13.7) in favor of SIT. A 3-year course of SIT with standardized allergen extracts has shown long-term clinical effects and the potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment. Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.
STUDY QUESTION
Which genes and molecular mechanisms are involved in the human ovulatory cascade and final oocyte maturation?
SUMMARY ANSWER
Up-regulated genes in granulosa cells (GC) represented ...inflammation, angiogenesis, extracellular matrix, growth factors and genes previously associated with ovarian cancer, while down-regulated genes mainly represented cell cycle and proliferation.
WHAT IS KNOWN ALREADY
Radical changes occur in the follicle during final follicle maturation after the ovulatory trigger: these range from ensuring an optimal milieu for the oocyte in meiotic arrest to the release of a mature oocyte and remodeling into a corpus luteum. A wide range of mediators of final follicle maturation has been identified in rodents, non-human primates and cows.
STUDY DESIGN, SIZE, DURATION
Prospective cohort study including 24 women undergoing ovarian stimulation with the long gonadotrophin-releasing hormone agonist protocol during 2010–2012 at Holbæk Fertility Clinic. Nine paired samples of GC and 24 paired samples of follicular fluid (FF) were obtained before and after recombinant human chorionic gonadotrophin (rhCG) administration.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Nine paired (nine arrays before rhCG and nine arrays after rhCG) samples of GC mRNA were amplified and hybridized to Affymetrix Human Gene 1.0 ST GeneChip arrays, compared and bioinformatically analyzed. Eleven selected genes were validated by quantitative reverse transcriptase PCR. FF hormones were analyzed by enzyme-linked immunosorbent assay.
MAIN RESULTS AND THE ROLE OF CHANCE
Eleven hundred and eighty-six genes were differentially expressed (>2-fold, P<0.0001, false discovery rate <0.0012) when comparing GC isolated before and 36 h after hCG, among those were genes known to be expressed at ovulation, i.e. ADAMTS1 and HAS2. Many new ovulation-related genes were revealed, such as CD24, ANKRD22, CLDN11 and FBXO32. FF estrogen, androstenedione and anti-Müllerian hormone decreased significantly while progesterone increased, accompanied by radical changes in the expression of steroidogenic genes (CYP17A, CYP19A, HSD11B1 and HSD11B2, StAR). Genes related to inflammation, angiogenesis, extracellular matrix formation, growth factors and cancer were up-regulated while cell cycle genes were massively down-regulated. Seventy-two genes previously described in connection with ovarian cancer were among the highly regulated genes. In silico analysis for top upstream regulators of the ovulatory trigger suggested—besides LH—TNF, IGF1, PGR, AR, EGR1 (early growth response 1), ERK1/2 (extracellular signal regulated kinase 1/2) and CDKN1A (cyclin-dependent kinase inhibitor 1A) as potential mediators of the LH/hCG response.
LIMITATIONS, REASONS FOR CAUTION
The present dataset was generated from women under hormonal stimulation. However, comparison with a macaque natural cycle whole follicle ovulation dataset revealed major overlap, supporting the idea that the ovulation-related genes found in this study are relevant in the human natural cycle.
WIDER IMPLICATIONS OF THE FINDINGS
These data will serve as a research resource for genes involved in human ovulation and final oocyte maturation. Ovulation-related genes might be good candidate biomarkers of follicle and oocyte health. Further, some of the ovulation-related genes may serve as future ovarian cancer biomarkers.
STUDY FUNDING/COMPETING INTEREST(S)
Grants from the Research Fund of Region Sjælland are gratefully acknowledged. None of the authors declared any conflict of interest.
TRIAL REGISTRATION NUMBER
Not applicable.
Abstract
Background
Immediate diagnosis of acute decompensated heart failure (ADHF) is essential in patients with dyspnoea. Remote Dielectric Sensing (ReDS), an electromagnetic non-invasive ...technology, estimates lung fluid content fast and observer-independently. In previous studies, ReDS discriminated congested heart failure patients from normal subjects with high accuracy. But not all ADHF patients have pulmonary interstitial congestion in the real world, and it is unknown if ReDS detects ADHF in consecutive patients with acute dyspnoea.
Purpose
To examine if ReDS can detect ADHF in consecutive dyspnoeic emergency patients and to compare ReDS with other diagnostic methods.
Method
This prospective observational study included consecutive patients with dyspnoea from the emergency departments. The exclusion criteria were age below 50 years, acute coronary syndrome, conditions prohibiting a supine CT scan, and no informed consent. We examined all patients immediately with ReDS, low-dose chest CT, echocardiogram, lung ultrasound (LUS), NT-proBNP, and Boston score. The Boston score used chest X-ray and clinical signs such as orthopnoea, jugular venous elevation, lung crackles and pedal oedema, and a score ≥8 equalled definite ADHF. A “LUS-score” ≥3 with at least 3 B-lines in one zone bilaterally equalled ADHF. ReDS values >35% lung fluid content were positive for pulmonary congestion, according to previous studies.
According to ESC guidelines, an expert panel adjudicated the ADHF diagnosis based on clinical signs, chest X-ray image, NT-proBNP, echocardiographic cardiac dysfunction (HFvhd, HFrEF, HFmrEF, HFpEF), and elevated LV filling pressure. Importantly, the panel was blinded to the ReDS values. For sub-analyses, we divided ADHF patients into a “CT-congested” ADHF subgroup if an independent chest CT showed interstitial congestion. We classified ADHF patients without congestion on CT, as the “mildly-congested” subgroup.
Results
97 included patients were examined within a median of 4.8 hours from admittance: 39 (40%) had ADHF, and 25 (26%) were ReDS-positive. ADHF patients had median LVEF 48%, NT-proBNP 347 pmol/l, and 85% had echocardiographic elevated LV filling pressure. ReDS detected ADHF with 46% sensitivity, 88% specificity, and 71% accuracy. The AUC for ReDS to detect ADHF (Figure 1), on a continuous scale, was similar to the Boston score (p=0.88) and the LUS score (p=0.74), but lower than NT-proBNP (p=0.02). The 21 (22%) CT-congested ADHF patients had higher ReDS values than the 18 (19%) mildly-congested ADHF patients (Figure 2, median 38% vs 30%, p<0.001). Furthermore, the mildly-congested ADHF patients had ReDS values similar to non-ADHF patients (median 30% vs 28%, p=0.36).
Conclusion
ReDS detects ADHF similarly to the Boston score and lung ultrasound but is inferior to NT-proBNP. This study suggests that ReDS primarily identifies CT-congested ADHF patients, but not the ADHF patients without interstitial congestion.
Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): This work was supported by the research fund of Bispebjerg University Hospital and Holger & Ruth Hesse's Mindefond. Sensible Medical Ltd made the ReDS device available for free and provided an unrestricted grant to specifically collect the ReDS measurements. The sponsors did not affect the statistical analyses, study design, data collection, or writing of the paper.
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