The aim of this study was to assess the effect of living away from, or in, the family home on the dietary habits of a group of Greek undergraduate University students. Eighty-four undergraduates at ...Athens Agricultural University, aged 20–24, completed a single, self-administered food habits questionnaire that asked about their current food practices and their food practices before they started University. Students living at home did not show major changes in their eating habits since starting University. Although students living away from the family home had made some positive changes, they decreased their weekly consumption of fresh fruit, cooked and raw vegetables, oily fish, seafood, pulses and olive oil, and increased their sugar, wine, alcohol and fast food intake. Between group comparisons of dietary changes showed that since starting University, students living away from home had developed more unfavourable eating habits than students living at the family home. These findings suggest that moving away from the family home and assuming responsibility for food preparation and purchasing for the first time affect dietary habits in this sample of Greek University students. Nutrition interventions in this young population should be encouraged to promote healthier diets and lifestyles, as well as adherence to the traditional Mediterranean diet.
We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent ...lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)-class II expression on selected monocyte populations. Furthermore, decreased HLA-DR on intermediate monocytes predicted severe COVID-19 disease. In contrast to prevailing assumptions, very few (7 of 168) patients with COVID-19 exhibited cytokine profiles indicative of cytokine storm syndrome. After controlling for multiple factors including age and sample time point, patients with COVID-19 exhibited lower cytokine levels than patients with influenza. Up-regulation of IL-6, G-CSF, IL-1RA, and MCP1 predicted death in patients with COVID-19 but were not statistically higher than patients with influenza. Single-cell transcriptional profiling revealed profound suppression of interferon signaling among patients with COVID-19. When considered across the spectrum of peripheral immune profiles, patients with COVID-19 are less inflamed than patients with influenza.
Understanding the three-dimensional (3-D) micro-architecture of lung tissue can provide insights into the pathology of lung disease. Micro computed tomography (µCT) has previously been used to ...elucidate lung 3D histology and morphometry in fixed samples that have been stained with contrast agents or air inflated and dried. However, non-destructive microstructural 3D imaging of formalin-fixed paraffin embedded (FFPE) tissues would facilitate retrospective analysis of extensive tissue archives of lung FFPE lung samples with linked clinical data.
FFPE human lung tissue samples (n = 4) were scanned using a Nikon metrology µCT scanner. Semi-automatic techniques were used to segment the 3D structure of airways and blood vessels. Airspace size (mean linear intercept, Lm) was measured on µCT images and on matched histological sections from the same FFPE samples imaged by light microscopy to validate µCT imaging.
The µCT imaging protocol provided contrast between tissue and paraffin in FFPE samples (15 mm x 7 mm). Resolution (voxel size 6.7 µm) in the reconstructed images was sufficient for semi-automatic image segmentation of airways and blood vessels as well as quantitative airspace analysis. The scans were also used to scout for regions of interest, enabling time-efficient preparation of conventional histological sections. The Lm measurements from µCT images were not significantly different to those from matched histological sections.
We demonstrated how non-destructive imaging of routinely prepared FFPE samples by laboratory µCT can be used to visualize and assess the 3D morphology of the lung including by morphometric analysis.
Maternal anaemia is a global public health problem contributing to adverse maternal and perinatal outcomes. In addition to other risk factors, interbirth interval has been identified as a potentially ...modifiable risk factor of maternal anaemia. However, the current evidence for the association between interbirth interval and maternal anaemia remains inconclusive. Hence, this study examined the association between the interbirth interval and maternal anaemia in sub-Saharan Africa. We conducted a multinational cross-sectional study of interbirth interval (time between two singleton live births) and maternal anaemia (haemoglobin levels < 12 g/dl for non-pregnant women, < 11 g/dl for pregnant women) for 21 sub-Saharan African countries using the most recent nationally representative Demographic and Health Surveys, 2010-2017. A weighted multivariable fractional polynomial function was used to estimate the non-linear relationship between interbirth interval and maternal anaemia, considering interbirth interval as a continuous variable and adjusting for potential confounders. Analyses were stratified by reproductive classification (non-pregnant and pregnant women). There were 81,693 women included in the study (89.2% non-pregnant, 10.8% pregnant). Of all women, 32.2% were in their postpartum period. Overall, 36.9% of women had anaemia (36.0% of non-pregnant and 44.3% of pregnant women). Of the participants, 15% had a short interbirth interval (<24 months), and 16% had a long interbirth interval (greater than or equal to 60 months). We found that both short and longer interbirth intervals were associated with an increased risk of maternal anaemia in a dose-response fashion. Relatively a lower risk of maternal anaemia was observed between 24 and 40 months of interbirth intervals. Our findings suggest that both short and longer interbirth intervals were associated with an increased risk of maternal anaemia in sub-Saharan Africa.
Objective
This review examines evidence related to the potential impact of obesity on the cardiovascular health effects of fine particulate air pollution (PM2.5).
Methods
A PubMed search was ...conducted in December, 2013 and studies were included if they examined the relationship between PM2.5 and cardiovascular health as well as effect modification by obesity.
Results
One hundred twenty‐one citations were reviewed; three large prospective cohort studies and 14 panel studies with short‐term follow‐up met the above criteria. All three cohort studies reported stronger associations between PM2.5 and cardiovascular mortality among obese subjects and one reported a significant trend of increased risk with increased body mass index. Similarly, 11 of 14 panel studies reported stronger associations between PM2.5 and acute changes in physiological measures of cardiovascular health among obese subjects including outcomes such as blood pressure and arrhythmia. Although interactions were not always statistically significant, the consistent pattern of stronger associations among obese subjects suggests that obesity may modify the impact of PM2.5 on cardiovascular health.
Conclusions
Epidemiological evidence suggests that obesity may increase susceptibility to the cardiovascular health effects of PM2.5. This an important area of research as the public health impacts of air pollution could increase with increasing prevalence of obesity.
We sought to investigate the diagnostic yield and mutation spectrum in previously reported genes for early-onset epilepsy and disorders of severe developmental delay.
In 400 patients with these ...disorders with no known underlying aetiology and no major structural brain anomaly, we analysed 46 genes using a combination of targeted sequencing on an Illumina MiSeq platform and targeted, exon-level microarray copy number analysis.
We identified causative mutations in 71/400 patients (18%). The diagnostic rate was highest among those with seizure onset within the first two months of life (39%), although overall it was similar in those with and without seizures. The most frequently mutated gene was SCN2A (11 patients, 3%). Other recurrently mutated genes included CDKL5, KCNQ2, SCN8A (six patients each), FOXG1, MECP2, SCN1A, STXBP1 (five patients each), KCNT1, PCDH19, TCF4 (three patients each) and ATP1A3, PRRT2 and SLC9A6 (two patients each). Mutations in EHMT1, GABRB3, LGI1, MBD5, PIGA, UBE3A and ZEB2 were each found in single patients. We found mutations in a number of genes in patients where either the electroclinical features or dysmorphic phenotypes were atypical for the identified gene. In only 11 cases (15%) had the clinician sufficient certainty to specify the mutated gene as the likely cause before testing.
Our data demonstrate the considerable utility of a gene panel approach in the diagnosis of patients with early-onset epilepsy and severe developmental delay disorders., They provide further insights into the phenotypic spectrum and genotype-phenotype correlations for a number of the causative genes and emphasise the value of exon-level copy number testing in their analysis.
Abstract This article concerns development and use of patient-reported outcomes (PROs) in clinical trials to evaluate medical products. A PRO is any report coming directly from patients, without ...interpretation by physicians or others, about how they function or feel in relation to a health condition and its therapy. PRO instruments are used to measure these patient reports. PROs provide a unique perspective on medical therapy, because some effects of a health condition and its therapy are known only to patients. Properly developed and evaluated PRO instruments also have the potential to provide more sensitive and specific measurements of the effects of medical therapies, thereby increasing the efficiency of clinical trials that attempt to measure the meaningful treatment benefits of those therapies. Poorly developed andevaluated instruments may provide misleading conclusions or data that cannot be used to support product labeling claims. We review selected major challenges from Food and Drug Administration's perspective in using PRO instruments, measures, and end points to support treatment benefit claims in product labeling. These challenges highlight the need for sponsors to formulate desired labeling claim(s) prospectively, to acquire and document information needed to support these claim(s), and to identify existing instruments or develop new and more appropriate PRO instruments for evaluating treatment benefit in the defined population in which they will seek claims.
A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19). This systematic review synthesizes current data on thrombosis risk, prognostic ...implications, and anticoagulation effects in COVID-19. We included 37 studies from 4070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic. The current certainty of evidence is generally very low and continues to evolve.
Flap endonuclease (FEN1), essential for DNA replication and repair, removes RNA and DNA 5′ flaps. FEN1 5′ nuclease superfamily members acting in nucleotide excision repair (XPG), mismatch repair ...(EXO1), and homologous recombination (GEN1) paradoxically incise structurally distinct bubbles, ends, or Holliday junctions, respectively. Here, structural and functional analyses of human FEN1:DNA complexes show structure-specific, sequence-independent recognition for nicked dsDNA bent 100° with unpaired 3′ and 5′ flaps. Above the active site, a helical cap over a gateway formed by two helices enforces ssDNA threading and specificity for free 5′ ends. Crystallographic analyses of product and substrate complexes reveal that dsDNA binding and bending, the ssDNA gateway, and double-base unpairing flanking the scissile phosphate control precise flap incision by the two-metal-ion active site. Superfamily conserved motifs bind and open dsDNA; direct the target region into the helical gateway, permitting only nonbase-paired oligonucleotides active site access; and support a unified understanding of superfamily substrate specificity.
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► Structures and mutations of FEN1:DNA complexes reveal 5′ flap recognition mechanism ► FEN1 binds 100° bent DNA and unpaired 3′ flap, threading the 5′ end for specific incision ► FEN1 disorder-to-order transition on substrate DNA binding aligns active site ► Two nucleotides of the 5′ flap must unpair to productively position DNA in active site
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