Assisted Reproductive Technologies (ART) is increasingly used to help infertile couples to have children around the world. A number of studies have been published reporting an increased risk of major ...malformations in children born following ART, especially an increased incidence of epigenetic diseases (ED). This study aimed to assess the incidence of epigenetic diseases with affected imprinting genes in infants or children from pregnancies obtained through IVF/ICSI compared to infants or children from pregnancies obtained spontaneously.
This is a monocentric retrospective epidemiological study based on data from a French congenital malformations registry called REMERA (Registre des Malformations en Rhône-Alpes) which exhaustively monitors all pregnancies in Rhone-Alpes region, whatever their nature of onset (spontaneous pregnancies or pregnancies from ART). This registry collects all malformations, except minor malformations (EUROCAT), and all polymalformative syndromes concerning all fetuses and children born alive or not, from 20 weeks of pregnancy (or 22 weeks of amenorrhea) and all medical termination of pregnancy whatever the term. Inclusion criteria are all diagnoses of epigenetic diseases (ED) related to parental imprinting recorded in the period January 2006 to December 2015.
For each year, the total number of births (including stillbirths) was collected from the annual activity reports of the registry. The exhaustive number of cases of epigenetic diseases was known in the registry. Were collected the number of births resulting from ART pregnancies in the study population. This incidence of ED was compared between births from spontaneous pregnancies and those obtained through ART (IVF/ICSI) with a generalized linear model (GLM: binomial regression).
In total, 46 cases of epigenetic diseases were analyzed on the REMERA registry files from 2006 to 2015. 4 cases from the 46 analyzed cases were from pregnancies induced by ART. ART was a risk factor for epigenetic disease (OR = 2.9 1.06–8.22 (p = .039)). In ART-pregnancies there were 2 diagnoses: Beckwith-Wiedemann syndrome (BWS) (3 cases out of 4) and Silver-Russell syndrome (SRS) (1 out of 4).
Infants and children obtained through IVF/ICSI appear to be related to a higher risk of epigenetic diseases compared to naturally conceived children. The perspectives of this study are to raise awareness about the creation of registries of congenital malformations and genetic and epigenetic syndromes with systematic and strict reports of all the cases on all the French territory and thus to widen this study with a bigger cohort.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A better understanding of immune-related adverse events is essential for the early detection and appropriate management of these phenomena. We conducted an observational study of cases recorded at ...the French reference center for hypereosinophilic syndromes and in the French national pharmacovigilance database. Thirty-seven reports of eosinophilia induced by treatment with immune checkpoint inhibitors (ICIs) were included. The median range time to the absolute eosinophil count (AEC) peak was 15 4─139 weeks. The median AEC was 2.7 0.8─90.9 G/L. Eosinophil-related manifestations were reported in 21 of the 37 cases (57%). If administered, corticosteroids were always effective (n = 10 out of 10). Partial or complete remission of eosinophilia was obtained in some patients not treated with corticosteroids, after discontinuation (n = 12) or with continuation (n = 4) of the ICI. The AEC should be monitored in ICI-treated patients. If required by oncologic indications, continuation of ICI may be an option in asymptomatic hypereosinophilic patients, and in corticosteroid responders.
Neuralgic amyotrophy (NA) is a multifocal inflammatory neuropathy. Although the exact etiopathogenesis of the latter is unknown, the literature reports frequent associations with immunological events ...such as different infectious diseases. Our case reveals a rarely described etiology of NA. NA is mainly a clinical diagnosis. The etiology shown in our case study is interesting for the scientific community, because CMV is an ubiquitous disease. NA is frequently under-recognized and misdiagnosed. This is particularly common in the early phase of the disease, when neurologic signs have not yet developed.
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BFBNIB, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Although pulmonary events are considered to be frequently associated with malignant haemopathies, they have been sparsely studied in the specific context of myelodysplastic syndromes (MDS). We aimed ...to describe their different types, their relative proportions and their relative effects on overall survival (OS). We conducted a multicentre retrospective cohort study. Patients with MDS (diagnosed according to the 2016 WHO classification) and pulmonary events were included. The inclusion period was 1 January 2007 to 31 December 2017 and patients were monitored until August 2019. Fifty-five hospitalized patients were included in the analysis. They had 113 separate pulmonary events. Thirteen patients (23.6%) had a systemic autoimmune disease associated with MDS. Median age at diagnosis of MDS was 77 years. Median time to onset of pulmonary events was 13 months. Pulmonary events comprised: 70 infectious diseases (62%); 27 interstitial lung diseases (23.9%), including 13 non-specific interstitial pneumonias and seven secondary organizing pneumonias or respiratory bronchiolitis-interstitial lung diseases; 10 pleural effusions (8.8%), including four cases of chronic organizing pleuritis with exudative effusion; and six pulmonary hypertensions (5.3%). The median OS of the cohort was 29 months after MDS diagnosis but OS was only 10 months after a pulmonary event. The OS was similar to that of the general myelodysplastic population. However, the occurrence of a pulmonary event appeared to be either an accelerating factor of death or an indicator for the worsening of the underlying MDS in our study. More than a third of pulmonary events were non-infectious and could be systemic manifestations of MDS.
Necrophagous flies breeding on carcasses face high selection pressures and therefore provide interesting opportunities to study social adaptations. We postulated that gregariousness in necrophagous ...blow fly larvae is an adaptive response to the environmental constraints of fresh carcasses. Cooperation is indeed believed to be key to the global success of social species. To test this idea, the development of Lucilia sericata (Diptera: Calliphoridae) larvae growing on low- or high-digestibility food substrate (control or trypsin-added ground beef muscle, respectively) at different larval densities was monitored. Results showed that larvae developed faster and had decreased mortality at high than low larval density. Furthermore, aggregation had no deleterious effect on the morphological characteristics (e.g. size) of postfeeding larvae and adult flies. We concluded that increased density positively affected population fitness, which is a conclusion consistent with the predictions of the Allee effect. Compared with those fed on regular food, larvae fed on high-digestibility food had reduced mortality and faster development on average. From these results, we postulated that collective exodigestion might be an adaptive response allowing blow flies to colonize fresh carcasses before the arrival of other insects and the multiplication of microbes. This hypothesis is consistent with the idea that cooperation may enable species to expand their niches.
•Gregariousness is an adaptive strategy of blowflies that breed on fresh carcasses.•Aggregation of necrophagous larvae reduces larval mortality and development time.•Larval behaviour is a social response to the environmental constraints of a carcass.•Results are consistent with the Allee effect (favourable selection of cooperation).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Heterospecific aggregations and foraging associations have been observed between different species, from apes to birds to insects. Such associations are hypothesized to result in a mutually ...beneficial relationship entailing benefits that are not apparent in conspecific groupings. Therefore, the objectives of the present study were to investigate 1) how 3 blowfly species, namely, Calliphora vicina, Calliphora vomitoria, and Lucilia sericata, aggregate according to species, and 2) if developmental benefits are linked to heterospecific aggregation. For objective (1), larvae of 2 species were placed between 2 conspecific aggregates, each with a different species (i.e., a binary choice test). After 20 h, the positions of all larvae were determined. On average, 98% of the maggots added later settled together on one of the 2 pre-existing aggregations, demonstrating a collective choice. The aggregation spot with C. vicina was preferred against others, indicating different attractiveness of different species. To relate this behavior to its benefits (objective ii), C. vicina and L. sericata larvae were raised from first instar to adult in con- and heterospecific conditions, and their development time, mortality rates, and morphometrics were measured. Thereby, mutual and asymmetric consequences were observed: specifically, there were significant increases in size and survival for L. sericata and faster development for C. vicina in heterospecific groups. These results indicate that the predilection for heterospecific association leads to mutual developmental benefits. This heterospecific aggregation behavior may be a resource-management strategy of blowflies to face carrion-based selection pressure.
Proteomics is continually being applied to a wider range of applications, now including the analysis of archaeological samples and anatomical specimens, particularly collagen-containing tissues such ...as bones and teeth. Here, we present the application of a chemical digestion-based proteomics sample preparation protocol to the analysis of fresh, anatomical, and archaeological samples. We describe and discuss two protocols: one that uses hydroxylamine as an additional step of the proteomic workflow, applied to the insoluble fraction, and another that applies hydroxylamine directly on demineralized bones and teeth. We demonstrate the additional information that can be extracted using both protocols, including an increase in the sequence coverage and number of peptides detected in modern and archaeological samples and an increase in the number of proteins identified in archaeological samples. By targeting research related to collagens or extracellular matrix proteins, the use of this protocol will open new insights, considering both fresh and ancient mineralized samples.
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IJS, KILJ, NUK, PNG, UL, UM
The recently described vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by somatic mutations in UBA1. Patients with VEXAS syndrome display late-onset ...autoinflammatory symptoms, usually refractory to treatment, and hematologic abnormalities. The identification of an easily-accessible specific marker (UBA1 mutations) is of particular interest as it allows the convergence of various inflammatory and hematological symptoms in a unique clinico-biological entity and gives the opportunity to design specific treatment strategies. Here we retrospectively identified 6 patients with VEXAS syndrome who underwent allogeneic hematopoietic stem cell transplantation (ASCT). To date, no treatment guidelines have been validated. In 4 patients, ASCT was guided by life-threatening autoinflammatory symptoms that were refractory to multiple therapies. Three patients are in durable complete remission 32, 38, and 37 months after ASCT. Two others are in complete remission response after 3 and 5 months. One unfortunately died post-ASCT. This report suggests that ASCT could be a curative option in patients with VEXAS syndrome and severe manifestations. Considering the complications and side effects of the procedure as well as the existence of other potential treatment, clinical trials are needed to define the subgroup of patients who will benefit from this strategy and its place in the therapeutic arsenal against VEXAS syndrome.
•Allogeneic hematopoietic stem cell transplantation is a curative option in patients with VEXAS syndrome and severe manifestations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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