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Evidence regarding the analgesic effect of distraction through immersion in virtual reality (VR) for care-induced pain has been documented in several phase 2 trials, but comparison with standard treatments in large, randomized studies is needed. In this open-label, multicenter, randomized, phase 3 trial, we evaluated the safety and efficacy of a novel VR therapy solution for distraction in the context of bone marrow biopsy. Bliss is a VR software with 4 imaginary interactive environments in 3 dimensions with binaural sound (head-mounted display). Efficacy regarding pain intensity was evaluated using a visual analog scale (VAS; score from 0 to 10) immediately after the biopsy. Secondary end points were anxiety and tolerance. Modified intention-to-treat analysis was performed. Overall, 126 patients with previously documented untreated or suspected malignant hemopathy between September 6, 2018, and May 18, 2020, were randomly assigned in a 1:1 ratio to receive pain prevention with a mixture of nitrous oxide/oxygen (MEOPA; n=63) or VR (n=63) before and during the bone marrow biopsy. We excluded 8 patients from the final analysis (3 in the MEOPA group and 5 in the VR group). All patients received local anesthesia (lidocaine) before biopsy. Follow-up was limited to 1 month after the biopsy. Participants' median age was 65.5 (range 18-87) years, and 54.2% (64/118) of patients were male. The average pain intensity was 3.5 (SD 2.6, 95% CI -1.6 to 8.6) for the MEOPA group and 3.0 (SD 2.4, 95% CI -1.7 to 7.7) for the VR group, without any significant differences in age, sex, center, and hemopathy (P=.26). Concerning anxiety, 67.5% (79/117; fear of pain questionnaire) of the patients were afraid before the biopsy, and anxiety scores were moderate to very high in 26.3% (30/114; revised Spielberger State-Trait Anxiety Inventory questionnaire) of the patients before the biopsy and 9.0% (10/114) after the biopsy for all patients, without a significant difference between the 2 groups (P=.83). Immersion in VR was well tolerated by the majority (54/57, 95%) of patients in the VR group. The intensity of pain did not significantly differ between both arms. VR was well tolerated, and the satisfaction of patients, nurses, and physicians was very high. VR could be an alternative treatment in case of contraindication or intolerance to MEOPA. ClinicalTrials.gov NCT03483194; https://clinicaltrials.gov/ct2/show/NCT03483194.

PurposeTo qualify the quality of patients sexual lives after treatment among women with breast cancer under 35 years old and compare results to the literature.MethodsSexual quality of life was measured for 84 women aged 20 to 35 years old at diagnosis, with two validated quality of sexual life questionnaires, Brief Index of Sexual Functioning for Women (BISF-W) and Female Sexual Function Index (FSFI), at least six months after breast cancer diagnosis. Two other questionnaires were used to allow us to understand other aspects of their life before cancer and to monitor quality of sexual life during treatment.ResultsForty-three women responded to the questionnaire. The questionnaires demonstrated that more than half of them had problems with their sexuality. The mean total score was 28.08/75 for BISF-W and 25.1 for FSFI (under the cutoff score 26.55). The domain analysis showed an association between the absence of chemotherapy and scores in regard to sexual health. Only 7% had sexual disturbance detected but 49% of the patients wished to have it.ConclusionSexual dysfunction in breast cancer survivors is real, has several factors, and cannot be evaluated based only on the organic side effects induced by cancer treatment. Better monitoring and screening seems necessary in order to optimize the quality of sexual life after surviving breast cancer.

PurposeTotally implantable venous access ports (TIVAP) have been widely used for many years in the management of patients suffering from cancer. The implantation and long-term use of TIVAPs are associated with mechanical, thrombotic, and infectious complications. This is the first exhaustive prospective study of all complications occurring in a whole population on long-term follow-up and therefore allows an objective assessment to be made of the safety of TIVAPs.MethodsWe carried out a prospective single-center observational study. All adult patients with cancer who had a TIVAP implanted between January 1 and December 31, 2006 were registered. Early and late complications were recorded until the removal of the device, the patient’s death, or until December 31, 2013. Exhaustive data concerning patients and TIVAP was recorded at time of implantation.ResultsFour hundred and ninety-three TIVAPs were implanted in 483 adult cancer patients and were followed during a period from 1 to 94 months (median = 18 months) representing a global quantity of 367,359 catheter-days. Eighty-seven complications were recorded (0.237/1000 catheter-days), including 37 infections (0.101/1000 catheter-days), 17 thrombotic events (0.046/1000 catheter-days), and 9 extravasations. Out of the 87 events, 62 (71.3%) occurred during the first year after implantation. Events were therefore extremely rare after 1 year. Thromboembolic and infectious complications were rare and no risk factors for these were found.ConclusionsThis study demonstrates excellent tolerability, with only occasional complications. Most of these occurred during the year following implantation. A TIVAP may also be left in place for an extremely long time.

The effects of maternal vitamin B-6 deficiency on concentrations of the neurotransmitters, (gamma)-aminobutyric acid (GABA) and dopamine (DA), and sixteen amino acids in specific regions, substantia nigra (SN), caudate/putamen (C/P), cortex (CORT), were studied in 15-day-old progeny. These measurements were examined in relation to synapse counts and neuronal density in C/P of progeny. Two strains of female rats, Wistar (group I) and Sprague-Dawley (group II), were fed either a deficient (0.6 mg pyridoxine(.)HCl (PN(.)HCl) diet) or control (7.0 mg PN(.)HCl/kg diet) diet from weaning throughout gestation and lactation. Analyses of brain regions of progeny were made at 15 days of age generally after gross neurological symptoms appeared in deficient groups. Biochemical alterations observed in the deficient animals included increased concentrations of cystathionine, glycine, methionine, phenylalanine, leucine, isoleucine and valine and decreased concentrations of alanine and serine in all brain regions studied (SN, C/P, CORT) and with some noticeable regional differences. GABA concentrations were decreased in C/P of deficient animals from group I compared to control values whereas concentrations of aspartic acid, glutamic acid or DA were not affected by the deficiency in any region studied. At 1 hr following an intraperitoneal injection of PN(.)HCl into deficient progeny, a significant decrease was observed in glutamic acid in C/P and a significant increase of aspartic acid in SN. Additionally, GABA levels were increased significantly in SN within 3 hr post-injection. Since glutamic acid is a precursor of both aspartic acid and GABA, these findings indicated the involvement of vitamin B-6 in strionigral connections. Following PN(.)HCl injection increased GABA concentrations in SN may compensate for the significant increases of DA observed in C/P at 1 and 3-hr post-injection. Morphological changes associated with the biochemical changes included decreased numbers of synapses and increased neuronal density in C/P of deficient pups compared to control values.

CRISPR/Cas9 has revolutionized our ability to engineer genomes and conduct genome-wide screens in human cells 1 – 3 . Whereas some cell types are amenable to genome engineering, genomes of human pluripotent stem cells (hPSCs) have been difficult to engineer, with reduced efficiencies relative to tumour cell lines or mouse embryonic stem cells 3 – 13 . Here, using hPSC lines with stable integration of Cas9 or transient delivery of Cas9-ribonucleoproteins (RNPs), we achieved an average insertion or deletion (indel) efficiency greater than 80%. This high efficiency of indel generation revealed that double-strand breaks (DSBs) induced by Cas9 are toxic and kill most hPSCs. In previous studies, the toxicity of Cas9 in hPSCs was less apparent because of low transfection efficiency and subsequently low DSB induction 3 . The toxic response to DSBs was P53/TP53 -dependent, such that the efficiency of precise genome engineering in hPSCs with a wild-type P53 gene was severely reduced. Our results indicate that Cas9 toxicity creates an obstacle to the high-throughput use of CRISPR/Cas9 for genome engineering and screening in hPSCs. Moreover, as hPSCs can acquire P53 mutations 14 , cell replacement therapies using CRISPR/Cas9-enginereed hPSCs should proceed with caution, and such engineered hPSCs should be monitored for P53 function. CRISPR–Cas9-induced DNA damage triggers p53 to limit the efficiency of gene editing in human pluripotent cells.

Given the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded. The study of pollen loads of insects captured in plant communities revealed that as compared to the observation of visits, metabarcoding revealed 2.5 times more plant species involved in plant-pollinator interactions. We further observed a tight positive relationship between the pollen-carrying capacities of insect taxa and the number of trnL and ITS1 sequences. The number of visits received per plant species also positively correlated to the number of their ITS1 and trnL sequences in insect pollen loads. By revealing interactions hard to observe otherwise, metabarcoding significantly enlarges the spatiotemporal observation window of pollination interactions. By providing new qualitative and quantitative information, metabarcoding holds great promise for investigating diverse facets of interactions and will provide a new perception of pollination networks as a whole.

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for patients with myeloid/lymphoid neoplasm (MLN) with FGFR1 rearrangement, but data on overall results are limited. We report on the largest series of patients (n = 22) with FGFR1-rearranged MLN undergoing allo-HCT. Distribution according to cytogenetic subtype was: t(8;13) in 11 cases, t(8;22) in 7 cases, t(6;8) in 2 cases, and other (n = 2). Over a third of patients displayed a chronic myeloproliferative (MPN) phenotype, another third showed MPN features with concomitant lymphoma or acute leukemia, and the remaining ones presented as acute leukemia. After a median follow-up of 4.1 years from transplant, the estimated 5-year survival rate, progression-free survival, non-relapse mortality and relapse incidence was 74%, 63%, 14% and 23%, respectively. Causes of death were relapse/progression (n = 4), graft-versus-host disease (n = 2) and organ toxicity (n = 1). Six patients experienced disease relapse at a median of 6.1 months (range: 2.3–119.6). Two of them achieved complete remission with ponatinib or pemigatinib and were alive at 34.5 and 37 months from relapse, respectively. These data highlight the significant curative potential of allo-HCT in this aggressive disease. Maintenance with tyrosine kinase inhibitors may be a promising approach, at least in cases with detectable residual disease after transplant.

We aimed to evaluate the determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) and to describe factors predicting the main post-HCT complications. This retrospective study by the European Society for Blood and Marrow Transplantation included 2916 myelofibrosis patients who underwent first allo-HCT from an HLA-identical sibling or unrelated donor between 2000 and 2016. After a median follow-up of 4.7 years from transplant, projected median survival of the series was 5.3 years. Factors independently associated with increased mortality were age ≥ 60 years and Karnofsky Performance Status <90% at transplant, and occurrence of graft failure, grades III–IV acute graft-vs.-host disease (aGVHD), and disease progression/relapse during follow-up. The opposing effects of chronic graft-vs.-host disease (GVHD) on non-relapse mortality and relapse incidence resulted in a neutral influence on survival. Graft failure increased in unrelated donor recipients and decreased with myeloablative conditioning (MAC) and negative donor/recipient cytomegalovirus serostatus. Risk of grades III–IV aGVHD was higher with unrelated donors and decreased with MAC. Relapse incidence tended to be higher in patients with intermediate-2/high-risk DIPSS categories and to decrease in CALR -mutated patients. Acute and chronic GVHD reduced the subsequent risk of relapse. This information has potential implications for patient counseling and clinical decision-making.

Many studies have shown effects of plants species on fungal communities, but these are often confounded with soil effects. Thus, the specific role of plant species in structuring rhizospheric and soil fungal communities is poorly described. Our study used microcosms in which plants were grown under artificial conditions to bridge this gap. Two perennial grasses dominating subalpine grasslands, Festuca paniculata and Dactylis glomerata, were grown at two levels of fertilization on standard soil. Fungal communities were determined by 454 pyrosequencing of the internal transcribed spacer 1 region. Among the fungal communities characterized by the primers used, original communities were associated to each plant species and also diverged between rhizosphere and bulk soils within each plant species, though there were no significant fertilization effects. Differences regarded global composition of the fungal communities and abundant molecular operational taxonomic units (MOTUs). Both plant species and location effects were reflected more in the abundance than in the composition of MOTUs. The observed differences in fungal communities coincide with differing strategies of plant root growth, with D. glomerata having greater root mass, length, and area than F. paniculata. Our study, by dissociating soil effects from plant effects, demonstrated that plant species exert a key control on soil fungi. We suggest that such effects may be linked to inter-specific differences in root traits and their consequences on nitrogen uptake.