The problem of assessing the quality of health

This article analyzes the concept of "health" and the problem of assessing the quality of health

SARS-CoV-2 infection among hospitalised pregnant women and impact of different viral strains on COVID-19 severity in Italy: a national prospective population-based cohort study

OBJECTIVE: The primary aim of this article was to describe SARS-CoV-2 infection among pregnant women during the wild-type and Alpha-variant periods in Italy. The secondary aim was to compare the impact of the virus variants on the severity of maternal and perinatal outcomes. DESIGN: National population-based prospective cohort study. SETTING: A total of 315 Italian maternity hospitals. SAMPLE: A cohort of 3306 women with SARS-CoV-2 infection confirmed within 7 days of hospital admission. METHODS: Cases were prospectively reported by trained clinicians for each participating maternity unit. Data were described by univariate and multivariate analyses. MAIN OUTCOME MEASURES: COVID-19 pneumonia, ventilatory support, intensive care unit (ICU) admission, mode of delivery, preterm birth, stillbirth, and maternal and neonatal mortality. RESULTS: We found that 64.3% of the cohort was asymptomatic, 12.8% developed COVID-19 pneumonia and 3.3% required ventilatory support and/or ICU admission. Maternal age of 30-34 years (OR 1.43, 95% CI 1.09-1.87) and ≥35 years (OR 1.62, 95% CI 1.23-2.13), citizenship of countries with high migration pressure (OR 1.75, 95% CI 1.36-2.25), previous comorbidities (OR 1.49, 95% CI 1.13-1.98) and obesity (OR 1.72, 95% CI 1.29-2.27) were all associated with a higher occurrence of pneumonia. The preterm birth rate was 11.1%. In comparison with the pre-pandemic period, stillbirths and maternal and neonatal deaths remained stable. The need for ventilatory support and/or ICU admission among women with pneumonia increased during the Alpha-variant period compared with the wild-type period (OR 3.24, 95% CI 1.99-5.28). CONCLUSIONS: Our results are consistent with a low risk of severe COVID-19 disease among pregnant women and with rare adverse perinatal outcomes. During the Alpha-variant period there was a significant increase of severe COVID-19 illness. Further research is needed to describe the impact of different SARS-CoV-2 viral strains on maternal and perinatal outcomes

eIF5A Promotes Translation Elongation, Polysome Disassembly and Stress Granule Assembly

Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate in cells exposed to environmental stress. We have identified ornithine decarboxylase (ODC), an enzyme required for polyamine synthesis, and eIF5A, a polyamine (hypusine)-modified translation factor, as proteins required for arsenite-induced SG assembly. Knockdown of deoxyhypusine synthase (DHS) or treatment with a deoxyhypusine synthase inhibitor (GC7) prevents hypusine modification of eIF5A as well as arsenite-induced polysome disassembly and stress granule assembly. Time-course analysis reveals that this is due to a slowing of stress-induced ribosome run-off in cells lacking hypusine-eIF5A. Whereas eIF5A only marginally affects protein synthesis under normal conditions, it is required for the rapid onset of stress-induced translational repression. Our results reveal that hypusine-eIF5A-facilitated translation elongation promotes arsenite-induced polysome disassembly and stress granule assembly in cells subjected to adverse environmental conditions

Tumour inoculation site-dependent induction of cachexia in mice bearing colon 26 carcinoma

Murine colon 26 carcinoma growing at either subcutaneous (s.c.) or intramuscular (i.m.) inoculation sites causes cachexia in mice. Such animals show extensive loss of body weight, wasting of the muscle and adipose tissues, hypoglycaemia, and hypercalcaemia, even when the tumour weight comprises only about 1.9% of carcass weight. In contrast, the same tumour when inoculated into the liver does not cause any sign of tumour-related cachexia even when the tumour becomes much larger (6.6% of carcass weight). Interleukin 6 (IL-6), a mediator associated with cachexia in this tumour model, is detected at high levels both in the tumour tissues and in the circulating blood of mice bearing colon 26 tumour at the s.c. inoculation site. In contrast, only minute levels of IL-6 are detected in the tumour grown in the liver. The colon 26 tumour grown in the liver does not lose its ability to cause cachexia, because the tumour when re-inoculated s.c. is able to cause extensive weight loss and produce IL-6 as did the original colon 26 cell line. Histological studies revealed differences in the composition of tumour tissues: the tumours grown in the subcutis consist of many polygonal tumour cells, extended-intercellular space, and high vascular density, whereas those grown in the liver consist of spindle-shaped tumour cells. Thus, the environment where tumour cells grow would be a critical factor in determining the cachectic phenotype of cancer cells, including their ability to produce IL-6. 1999 Cancer Research Campaig

Vaccination against SARS-CoV-2 in pregnancy during the Omicron wave: the prospective cohort study of the Italian obstetric surveillance system

Objectives: Evidence on the effects of the SARS-CoV-2 Omicron variant on vaccinated and unvaccinated pregnant women is sparse. This study aimed to compare maternal and perinatal outcomes of women infected with SARS-CoV-2 during the Omicron wave in Italy, according to their vaccine protection.Methods: This national prospective cohort study enrolled pregnant women with a positive SARS-CoV-2 nasopharyngeal swab within 7 days of hospital admission between 1 January and 31 May, 2022. Women who received at least one dose of vaccine during pregnancy and those who completed the vaccine cycle with the first booster were considered protected against moderate or severe COVID-19 (MSCD). A multivariable logistic regression model evaluated the association between vaccine protection and disease severity. Maternal age, educational level, citizenship, area of birth, previous comorbidities, and obesity were analysed as potential risk factors. Results: MSCD was rare (41/2147, 1.9%; 95% CI, 1.4-2.6), and the odds of developing it were significantly higher among unprotected women (OR, 2.78; 95% CI, 1.39-5.57). Compared with protected women (n = 1069), the unprotected (n = 1078) were more often younger, with lower educational degrees, and foreigners. A higher probability of MSCD was found among women with previous comorbidities (OR, 2.86; 95% CI, 1.34-6.12) and those born in Asian countries (OR, 3.05; 95% CI, 1.23-7.56). The percentage of preterm birth was higher among women with MSCD compared with milder cases (32.0% [8/25] versus 8.4% [161/1917], p < 0.001) as well as the percentage of caesarean section (52.0% [13/25] versus 31.6% [606/1919], p 0.029). Discussion: Although severe maternal and perinatal outcomes were rare, their prevalence was significantly higher among women without vaccine protection. Vaccination during pregnancy has the potential to protect both the mother and the baby, and it is therefore strongly recommended. Edoardo Corsi Decenti, Clin Microbiol Infect 2023;29:772 (c) 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk

IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1α and IL1β. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case–control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P=0.009). Evaluation of the prostate cancer risk associated with carrying the ‘ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR)=1.6, 95% confidence interval (CI)=1.2–2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR=1.0, 95% CI=0.8–1.2). Restricting analyses to advanced prostate cancer strengthened the association between the ‘ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI=1.3–2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association

Perinatal care in SARS-CoV-2 infected women: the lesson learnt from a national prospective cohort study during the pandemic in Italy

Background: Despite the growing importance given to ensuring high-quality childbirth, perinatal good practices have been rapidly disrupted by SARS-CoV-2 pandemic. This study aimed at describing the childbirth care provided to infected women during two years of COVID-19 emergency in Italy. Methods: A prospective cohort study enrolling all women who gave birth with a confirmed SARS-CoV-2 infection within 7 days from hospital admission in the 218 maternity units active in Italy during the periods February 25, 2020-June 30, 2021, and January 1-May 31, 2022. Perinatal care was assessed by evaluating the prevalence of the following indicators during the pandemic: presence of a labour companion; skin-to-skin; no mother-child separation at birth; rooming-in; breastfeeding. Logistic regression models including women' socio-demographic, obstetric and medical characteristics, were used to assess the association between the adherence to perinatal practices and different pandemic phases. Results: During the study period, 5,360 SARS-CoV-2 positive women were enrolled. Overall, among those who had a vaginal delivery (n = 3,574; 66.8%), 37.5% had a labour companion, 70.5% of newborns were not separated from their mothers at birth, 88.1% were roomed-in, and 88.0% breastfed. These four indicators showed similar variations in the study period with a negative peak between September 2020 and January 2021 and a gradual increase during the Alpha and Omicron waves. Skin-to-skin (mean value 66.2%) had its lowest level at the beginning of the pandemic and gradually increased throughout the study period. Among women who had a caesarean section (n = 1,777; 33.2%), all the indicators showed notably worse outcomes with similar variations in the study period. Multiple logistic regression analyses confirm the observed variations during the pandemic and show a lower adherence to good practices in southern regions and in maternity units with a higher annual number of births. Conclusions: Despite the rising trend in the studied indicators, we observed concerning substandard childbirth care during the SARS-CoV-2 pandemic. Continued efforts are necessary to underscore the significance of the experience of care as a vital component in enhancing the quality of family-centred care policies

Genetic aberrations in glioblastoma multiforme: translocation of chromosome 10 in an O-2A-like cell line

We have examined the genetic aberrations in two near-diploid glioblastoma multiforme cell lines that appear to have arisen from different glial lineages. One cell line, Hu-O-2A/Gb1, expresses antigens and metabolic profiles characteristic of the oligodendrocyte-type-2 astrocyte (0-2A) lineage of the rat central nervous system. This line generates, in vitro, cells with characteristics of 0-2A progenitor cells, oligodendrocytes and astrocytes. The second cell line, IN1434, is derived from an astrocyte or a precursor cell restricted to astrocytic differentiation. In Hu-O-2A/Gb1 the sole homologue of chromosome 10 is disrupted at band 10p11–12.1 by translocation with chromosomes X and 15. The translocation breakpoint is localized between genetic markers D10S2103 and [D10S637, D10S1962, D10S355]. Other aberrations include a 5;14 translocation, deletion of the long and short arms of chromosome 16 and loss of one copy of the CDKN2 gene. IN1434 cells share some cytogenetic abnormalities with Hu-O-2A/Gb1 cells, despite their apparent derivation from a different biological origin, but also have translocations involving the long and short arms of chromosome 1 and the long arm of chromosome 7, and deletion of chromosome 13 at bands 13q12–21. © 1999 Cancer Research Campaig

Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasmacytoid dendritic cell recruitment into the lungs and T cell priming

Rationale Sepsis, a global health burden, is often complicated by viral infections leading to increased long-term morbidity and mortality. Interleukin-3 (IL-3) has been identified as an important mediator amplifying acute inflammation in sepsis; however, its function in the host response to viral infections during sepsis remains elusive. Objectives To investigate the role of IL-3 during viral pneumonia in sepsis. Methods We included septic patients from two different cohorts and used in vitro and in vivo assays. The obtained data were substantiated using a second model (SARS-CoV-2 infections). Measurements and main results Low plasma IL-3 levels were associated with increased herpes simplex virus (HSV) airway infections in septic patients, resulting in reduced overall survival. Likewise, Il-3-deficient septic mice were more susceptible to pulmonary HSV-1 infection and exhibited higher pulmonary inflammation than control mice. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating plasmacytoid dendritic cells (pDCs) into the airways and by enhancing pDC-mediated T cell activation upon viral stimulation. Interestingly, the ability of IL-3 to improve adaptive immunity was confirmed in patients with SARS-CoV-2 infections. Conclusion Our study identifies IL-3 as a predictive disease marker for viral reactivation in sepsis and reveals that IL-3 improves antiviral immunity by enhancing the recruitment and the function of pDCs