Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Breeders Age Affects Reproductive Success in Nothobranchius furzeri

The present study was conducted to examine, for the first time in Nothobranchius furzeri, the effects of mating in different aged breeders with particular emphasis on reproductive fitness and the effects of parental aging on offspring gametogenesis. In N. furzeri, the increase of maternal and paternal age is often a predictable indicator of the upcoming deterioration on their natural habitat (i.e., ephemeral puddles) during African dry season. We previously revealed that elderly parents respond to their physiological decline state by decelerating offspring's development and growth rate. In the present study, we focused on the effects of different age parents at the onset of female offspring's sexual maturity since interaction between growth and reproduction traits generally occurs in vertebrates and could represent a life strategy. For this purpose, four different age breeder groups were set up. The age-specific breeder differences in reproductive performance were examined by analyzing the reproductive age-related fitness, the gametogenesis process in F1 females by histology, the offspring oocytes quality analyzing the gene expression of age-related molecular markers, like sirt1 and foxo3a, and the biochemical composition of vitellogenic oocytes using a spectroscopic approach. Results suggest that both maternal and paternal age affect reproductive performance and could influence the onset of sexual maturity in female offspring. In conclusion, these findings highlighted the effects of parental aging on life history traits in the short-lived model N. furzeri. Our results suggested that the advanced sexual maturity in offspring from young parents could be related to an adaptive response to the temporary habitat conditions

Effects of Parental Aging During Embryo Development and Adult Life: The Case of Nothobranchius furzeri

Studies on parental aging are a very attractive field, although it is poorly understood how parental age affects embryonic development and adult traits of the offspring. In this study, we used the turquoise killifish Nothobranchius furzeri, as is the vertebrate with shortest captive lifespan and an interesting model. The embryos of N. furzeri can follow two distinct developmental pathways either entering diapause or proceeding through direct development. Thus, this embryonic plasticity allows this model to be used to study different factors that could affect their embryonic development, including parental age. The first goal of the present study was to investigate whether parental aging could affect the embryo development. To do this, we collected F1 embryos from two breeder groups (old parents and young parents). We monitored the duration of embryonic development and analyzed genes involved in dorsalization process. The second goal was to investigate if embryonic developmental plasticity could be modulated by an epigenetic process. To this end, the expression of DNMTs genes was examined. Our data support the hypothesis that diapause, occurring more frequently in embryos from old parents, is associated with increased expression of DNMT3A and DNMT3B suggesting an epigenetic control. Finally, we analyzed whether parental age could affect metabolism and growth during adult life. Morphometric results and qPCR analysis of genes from IGF system showed a slower growth in adults from old breeders. Moreover, a gender-specificity effect on growth emerged. In conclusion, these results may contribute to the better understanding of the complex mechanism of aging

Effects of age on growth in Atlantic bluefin tuna

Atlantic Bluefin Tuna Thunnus thynnus (ABFT) is considered one of the most important socio-economic species but there is a lack of information on the physiological and molecular processes regulating its growth and metabolism. In the present study, we focused on key molecules involved in growth process. The aim of the present study was to associate molecular markers related to growth with canonical procedures like morphological measurements such as curved fork length (CFL) and round weight (RWT). The ABFT specimens (n=41) were organized into three different groups A, B and C according to their age. The molecular analysis of liver samples revealed that igf1, igf1r and mTOR genes, involved in growth process, were differentially expressed in relation to the age of the fish. In addition, during the analyzed period, faster growth was evident from 5 to 8 years of age, after that, the growth rate decreased in terms of length yet increased in terms of adipose tissue storage, as supported by the higher fat content in the liver. These results are useful in expanding basic knowledge about the metabolic system of ABFT and provide new knowledge for the aquaculture industry

Determination of Hg in Farmed and Wild Atlantic Bluefin Tuna (<i>Thunnus thynnus</i> L.) Muscle

Mercury (Hg) is a well-known toxic element, diffused in the environment, especially in the Mediterranean Sea which is rich in cinnabar deposits. Mercury bioaccumulation in fish is of great concern, especially for top-level aquatic predators (e.g., shark, tuna, swordfish) and above all for species of large human consumption and high nutritional value. This work aimed to determine Hg concentrations in farmed and wild Atlantic Bluefin tuna (Thunnus thynnus) caught in the Mediterranean area in order to evaluate the level of Hg bioaccumulation. selenium (Se) content was also determined, since this element is an antagonist of mercury toxicity. Mercury and Se were analysed by atomic absorption spectrometry after microwave digestion of the samples. Hg content in farmed tuna was below the legal limit (1 mg/kg, wet weight, w.w.) for all specimens (0.6 &#177; 0.2 mg/kg), whereas the wild ones had a content over the limit (1.7 &#177; 0.6 mg/kg); Se concentration was higher in farmed specimens (1.1 &#177; 0.9 mg/kg) compared to wild ones (0.6 &#177; 0.3 mg/kg). A safe seafood could show a Se/Hg ratio &gt;1 and a health benefit value (HBVSe) &gt; 0: farmed tuna had higher values than the wild specimens (Se/Hg 5.48 vs. 1.32; HBVSe 11.16 vs. 0.29). These results demonstrate that for Hg, there is a better risk/benefit ratio in farmed T. thynnus. making it safer than wild tuna

Determination of Hg and Se levels in Atlantic Bluefin Tuna (Thunnus thynnus L.) muscle: evaluation of the potential health risk/benefit for human.

Mercury and Selenium represent two key elements for human: the first is a well-known toxic element (1) whereas the second one is an essential micronutrient, but also an antagonist of mercury toxicity (2). Due to these features, the knowledge about Hg and Se levels in the seafood, that represents one of the principal sources for human assumption of these elements, is recommended. Se/Hg molar ratio have been generally used for the evaluation of risks posed by Hg exposure from seafood consumption, but recently a new parameter, the Selenium Health Benefit Value (HBVSe), was introduced to better understand the quote of bioavailable Selenium that remains after its mercury-interaction (3,4). Atlantic Bluefin tuna (Thunnus thynnus) is a species of large interest for its high nutritional value and for its increasing commercial interest in the last years. This work aimed to determine Hg and Se concentrations in farmed tuna, sampled from the fish farm Fish and Fish Ltd (South– East of Malta), and to make a comparison with wild Thunnus thynnus caught in the Mediterranean Sea, to calculate the Se/Hg ratio and the HBVSe parameter: at our knowledge, this is the first study that calculate the HBVSe in farmed and wild Atlantic Bluefin tuna from the Mediterranean Sea. Mercury was analysed by Direct Mercury Analyzer DMA-1, whereas Selenium was determined by Graphite Furnace Atomic Absorption Spectrometry (AAS-GF) after microwave digestion of the muscle samples. Data were evaluated in relation to biometric parameters such as age, sex, weight, and length. Results showed that mercury content in all farmed specimens (0.61±0.20 mg/kg ww) was below the law limit (1 mg/kg ww), whereas the wild specimens have in most cases a Hg content over the limit (1.68±0.58 mg/kg ww) (Fig. 1). Selenium concentration was higher in farmed specimens (1.07±0.86 mg/kg ww) respect to wild ones (0.64±0.31 mg/kg ww). Selenium showed no relation with biometric parameters (due to its homeostatic regulation), whereas mercury concentration of wild specimens increased linearly with weight (r=0.5721, p<0.05). Concerning the risk/benefit values, a safe seafood could show a Se/Hg ratio >1, and a HBVSe >0. Se/Hg ratio and HBVSe of farmed tuna showed higher values (Fig. 2) than the wild specimens, with Se/Hg ratio of 5.48 vs 1.32, and HBVSe of 11.16 vs 0.29, respectively. These results demonstrated that, concerning mercury presence, farmed Atlantic Bluefin Tuna has a minor risk/benefit ratio, and it is safer than wild tuna. This study, the first in tuna from the Mediterranean Sea, paves the way to future studies on nutritional value of farmed fish even in the framework of Marine Strategy that aims to a good environmental status both for Descriptor 3 (The population of commercial fish species is healthy) and Descriptor 9. (Contaminants in seafood are below safe levels)

Novel Translational Read-Through–Inducing Drugs as a Therapeutic Option for Shwachman-Diamond Syndrome

Shwachman-Diamond syndrome (SDS) is one of the most commonly inherited bone marrow failure syndromes (IBMFS). In SDS, bone marrow is hypocellular, with marked neutropenia. Moreover, SDS patients have a high risk of developing myelodysplastic syndrome (MDS), which in turn increases the risk of acute myeloid leukemia (AML) from an early age. Most SDS patients are heterozygous for the c.183-184TA&gt;CT (K62X) SBDS nonsense mutation. Fortunately, a plethora of translational read-through inducing drugs (TRIDs) have been developed and tested for several rare inherited diseases due to nonsense mutations so far. The authors previously demonstrated that ataluren (PTC124) can restore full-length SBDS protein expression in bone marrow stem cells isolated from SDS patients carrying the nonsense mutation K62X. In this study, the authors evaluated the effect of a panel of ataluren analogues in restoring SBDS protein resynthesis and function both in hematological and non-hematological SDS cells. Besides confirming that ataluren can efficiently induce SBDS protein re-expression in SDS cells, the authors found that another analogue, namely NV848, can restore full-length SBDS protein synthesis as well, showing very low toxicity in zebrafish. Furthermore, NV848 can improve myeloid differentiation in bone marrow hematopoietic progenitors, enhancing neutrophil maturation and reducing the number of dysplastic granulocytes in vitro. Therefore, these findings broaden the possibilities of developing novel therapeutic options in terms of nonsense mutation suppression for SDS. Eventually, this study may act as a proof of concept for the development of similar approaches for other IBMFS caused by nonsense mutations

Novel Translational Read-through-Inducing Drugs as a Therapeutic Option for Shwachman-Diamond Syndrome

Shwachman-Diamond syndrome (SDS) is one of the most commonly inherited bone marrow failure syndromes (IBMFS). In SDS, bone marrow is hypocellular, with marked neutropenia. Moreover, SDS patients have a high risk of developing myelodysplastic syndrome (MDS), which in turn increases the risk of acute myeloid leukemia (AML) from an early age. Most SDS patients are heterozygous for the c.183-184TA&gt;CT (K62X) SBDS nonsense mutation. Fortunately, a plethora of translational read-through inducing drugs (TRIDs) have been developed and tested for several rare inherited diseases due to nonsense mutations so far. The authors previously demonstrated that ataluren (PTC124) can restore full-length SBDS protein expression in bone marrow stem cells isolated from SDS patients carrying the nonsense mutation K62X. In this study, the authors evaluated the effect of a panel of ataluren analogues in restoring SBDS protein resynthesis and function both in hematological and non-hematological SDS cells. Besides confirming that ataluren can efficiently induce SBDS protein re-expression in SDS cells, the authors found that another analogue, namely NV848, can restore full-length SBDS protein synthesis as well, showing very low toxicity in zebrafish. Furthermore, NV848 can improve myeloid differentiation in bone marrow hematopoietic progenitors, enhancing neutrophil maturation and reducing the number of dysplastic granulocytes in vitro. Therefore, these findings broaden the possibilities of developing novel therapeutic options in terms of nonsense mutation suppression for SDS. Eventually, this study may act as a proof of concept for the development of similar approaches for other IBMFS caused by nonsense mutations

SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation

Patients with cystic fibrosis are not reporting particularly sever outcomes upon SARS-CoV-2 infection. Here, the authors demonstrate decreased ACE2 levels is cystic fibrosis airway epithelia associated with impaired viral entry and replication