Spread of a New Parasitic B Chromosome Variant Is Facilitated by High Gene Flow

The B24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise Nem estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B24 diffusion both eastward and westward, with minor role for B24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER ("Fondo Europeo de Desarrollo" - European Regional Development Fund - ERDF) funds. MIMP was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación

Geographical Barriers Impeded the Spread of a Parasitic Chromosome

Parasitic supernumerary (B) chromosomes show high capability to spread across populations. But the existence of abrupt discontinuities in their distribution demands an explanation. The grasshopper Eyprepocnemis plorans plorans harbour supernumerary chromosomes in all natural populations hitherto analyzed from the Circum-Mediterranean region, with the single exception of the headwaters of the Iberian Segura River and several of its tributaries. To ascertain the causes of this distribution pattern, we analyze here the genetic structure of five natural populations collected in this zone (two +B and three -B), by means of ISSR markers. We found significant population structure, with two kinds of populations coinciding with +B and -B ones, separated by strong barriers to gene flow. This gives strong support to the hypothesis that the non-B populations precede B origin, and that B-carrying individuals from coastal zones have been able to colonize upstream areas, until geographical barriers (usually narrow canyons and arid areas surrounding them) impeded their advance.The authors received no specific funding for this work. Project applications have been rejected in 2012, 2013 and 2014

Place of death of people with conditions needing palliative care in the different autonomous communities (regions) of Spain

Fundamento. Conocer el lugar de fallecimiento por causas susceptibles de cuidados paliativos de personas residentes en España de 15 o más años de edad según la comunidad autónoma (CA), y cómo influyen las causas (oncológicas y no oncológicas). Método. Estudio transversal de base poblacional con análisis de los certificados médicos de defunción entre 2012 y 2015. Los efectos ajustados de las variables sociodemográficas, la CA y las causas sobre el lugar de fallecimiento se estimaron mediante las odds de fallecimiento en hospital frente a domicilio (OH/D) y en residencia frente a domicilio (OR/D), y las odds ratio (ORH/D y ORR/D) obtenidas por regresión logística multinomial. Resultados. Se produjeron 1.611.767 muertes de las que 64,8% correspondieron a la población diana. La defunción en hospital fue un 77% más frecuente que en domicilio, y en residencia un 53% menor. Sexo masculino, menor edad, bajo nivel de estudios, lugar de nacimiento fuera de España, tamaño de municipio grande y estado civil no casado se asociaron a fallecimiento en hospital, y las mismas excepto sexo femenino y mayor edad a residencia. Las OH/D ajustadas fueron > 1 en todas las CA y las OR/D 1 and ON/H < 1 were observed in all AC, except Catalonia. Oncological causes made OH/H < 1 in almost 50% of AC, while ON/H continue to be < 1. Conclusions. Most deaths were in hospital and fewer at nursing homes, despite oncological causes increasing deaths at home (adjusted effect)

Single fetal demise in monochorionic twins: how to predict cerebral injury in the survivor co-twin?

The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury. Material and methods: Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012–2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development. Results: A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty-five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy-group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04–1.41, p = 0.014) and was higher in those surviving co-twins who developed anemia (OR 9.27, 95% CI: 1.50–57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68–11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome. Conclusions: Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co-twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurityThis study has been funded by “Instituto de Salud Carlos III” (ISCIII) through the project 19/00904, and co-funded by the European Union

A novel role for the tumor suppressor gene itf2 in tumorigenesis and chemotherapy response

Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million microarray-based comparative genomic hybridization (array-CGH) and qRT-PCR methodologies. RNA-sequencing, functional transfection assays, and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. The results were further explored in 55 lung and ovarian primary tumors and control samples, and in two extensive in silico databases. Long-term cell exposure to platinum induces the frequent deletion of ITF2 gene. Its expression re-sensitized tumor cells to platinum and recovered the levels of Wnt/β-catenin transcriptional activity. ITF2 expression was also frequently downregulated in epithelial tumors, predicting a worse overall survival. We also identified an inverse correlation between ITF2 and HOXD9 expression, revealing that Non-small cell lung cancer (NSCLC) patients with lower expression of HOXD9 had a better overall survival rate. We defined the implication of ITF2 as a molecular mechanism behind the development of cisplatin resistance probably through the activation of the Wnt-signaling pathway. This data highlights the possible role of ITF2 and HOXD9 as novel therapeutic targets for platinum resistant tumors.This research was funded by the Fondo de Investigación Sanitaria-Instituto de Salud Carlos III, PI15/00186 and PI18/00050, CP19/00063, and CM19/00100 for HR and by MINECO, RTC-2016-5314-1 to I.I.C; by the MINECO, SAF2016-75531-R, by the CAM B2017/BMD-3724 and by the AECC GCB14142311CRES to P.S; and the European Regional Development Fund/European Social Fund FIS (FEDER/FSE, Una Manera de Hacer Europa)

Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study

Grupo Español de Trasplante Hematopoyético (GETH) and Grupo Español de Linfoma y Trasplante Autólogo (GELTAMO).We performed a retrospective multicenter study including 140 patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) from March 1995 to November 2018. Our objective was to analyze long term outcomes. Seventy-four percent had received a previous auto-SCT (ASCT) and the median number of lines pre-allo-SCT was 3 (range 1–9). Three year-event free survival (EFS) and overall survival (OS) were 38% and 44%, respectively. Non-relapse mortality (NRM) at day 100 was 19%. Cumulative incidence of grade III–IV acute graft versus host disease (GVHD) at day 100 was 16% and moderate/severe chronic GVHD at 3 years 34%. Active disease at allo-SCT (HR 1.95, p = 0.039) (HR 2.19, p = 0.019), HCT-CI ≥ 2 (2.45, p = 0.002) (HR 2.33, p = 0.006) and donor age >37 years (HR 2.75, p = 0.014) (HR 1.98, p = 0.043) were the only independent variables both for PFS and OS, respectively. NRM was significantly modified by HCT-CI ≥ 2 (HR 4.8, p = 0.008), previous ASCT (HR 4.4, p = 0.048) and grade III–IV acute GVHD on day 100 (HR 6.13, p = 0.016). Our data confirmed that allo-SCT is a curative option for patients with R/R DLBCL, displaying adequate results for fit patients with chemosensitive disease receiving an allo-SCT from a young donor

Population Genetic Structure of the Grasshopper Eyprepocnemis plorans in the South and East of the Iberian Peninsula

The grasshopper Eyprepocnemis plorans subsp. plorans harbors a very widespread polymorphism for supernumerary (B) chromosomes which appear to have arisen recently. These chromosomes behave as genomic parasites because they are harmful for the individuals carrying them and show meiotic drive in the initial stages of population invasion. The rapid increase in B chromosome frequency at intrapopulation level is thus granted by meiotic drive, but its spread among populations most likely depends on interpopulation gene flow. We analyze here the population genetic structure in 10 natural populations from two regions (in the south and east) of the Iberian Peninsula. The southern populations were coastal whereas the eastern ones were inland populations located at 260–655 m altitude. The analysis of 97 ISSR markers revealed significant genetic differentiation among populations (average GST = 0.129), and the Structure software and AMOVA indicated a significant genetic differentiation between southern and eastern populations. There was also significant isolation by distance (IBD) between populations. Remarkably, these results were roughly similar to those found when only the markers showing low or no dropout were included, suggesting that allelic dropout had negligible effects on population genetic analysis. We conclude that high gene flow helped this parasitic B chromosome to spread through most of the geographical range of the subspecies E. plorans plorans.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER funds. MIMP was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación

Spread of a new parasitic B chromosome variant is facilitated by high gene flow

The B24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise Nem estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B24 diffusion both eastward and westward, with minor role for B24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population. © 2013 Manrique-Poyato et alThis study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER (>Fondo Europeo de Desarrollo> - European Regional Development Fund - ERDF) funds. MIMP was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación.Peer Reviewe

Place of death and associated factors: a population-based study using death certificate data

Background: Although studies suggest that most people prefer to die at home, not enough is known about place of death patterns by cause of death considering sociodemographic factors. The objective of this study was to determine the place of death in the population and to analyze the sociodemographic variables and causes of death associated with home as the place of death. Methods: Cross-sectional population-based study. All death certificate data on the residents in Spain aged 15 or over who died in Spain between 2012 and 2015 were included. We employed multinomial logistic regression to explore the relation between place of death, sociodemographic variables and cause of death classified according to the International Classification of Diseases, 10th revision, and to conditions needing palliative care. Results: Over half of all deaths occurred in hospital (57.4%), representing double the frequency of deaths that occurred at home. All the sociodemographic variables (sex, educational level, urbanization level, marital status, age and country of birth) were associated with place of death, although age presented the strongest association. Cause of death was the main predictor with heart disease, neurodegenerative disease, Alzheimer’s disease, dementia and senility accounting for the highest percentages of home deaths. Conclusions: Most people die in hospital. Cause of death presented a stronger association with place of death than sociodemographic variables; of these latter, age, urbanization level and marital status were the main predictors. These results will prove useful in planning end-of-life care that is more closely tailored to people’s circumstances and needs