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Abstract: Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy affecting young infants during early childhood. So far, the only cure for SCD involves hematopoietic stem cell transplantation (HCT). Recovery from this treatment represents a major change for the child and the child''s family. How do they deal with it? What are the consequences for the development of the young adolescent? To address these issues, we conducted a retrospective and multicentric research approach. Our study included 16 teenagers or young adults out of 28 patients. Two semi-structured interviews of either patients or patient''s families were carried out one year after HCT. Recovery is a complex process raising many questions and, therefore, requires an in-depth analysis. During patient''s adolescence, some questions related to recovery (disease transmission, identity issues) seem to reveal themselves. A psychiatric assessment should be recommended if psychological suffering appears or in the case of adolescent''s development delay or perturbation. [Copyright &y& Elsevier]

The objective of the study was to examine the process of mother to infant trauma transmission among traumatized mothers in humanitarian contexts. We investigated the impact of mothers' post-traumatic stress disorder symptoms on the quality of the dyadic interaction by conducting a microanalysis of mother-infant interactions at specific moments when trauma was recalled, compared to more neutral moments. Twenty-four mother-infant dyadic interactions of traumatized mothers and children aged from 1.5 to 30 months Central Africa, Chad, and Cameroon were videotaped during three sequences: a neutral initial session (baseline) exploring mothers' representations of the infant and of their bonding; a second sequence, "the traumatic narration," in which mothers were asked to talk about the difficult events they had experienced; and a third sequence focusing on a neutral subject. Three minutes of each sequence were coded through a specific grid for microanalysis [based on the scales developed at Bobigny Faculty of Medicine and the work of (1)], according to different communication modalities (touch, visual, and vocal), for both the mother and the child. Impact of traumatic event (IES-R), the level of depression and anxiety (HAD) were investigated in order to have a holistic understanding of the trauma transmission mechanism. The data analysis highlighted significant differences in mothers, children and their interaction during the "traumatic narration": mothers touched and looked at the infant less, looked more absent and smiled less, and looked less at the interviewer; infants looked less at the interviewer, and sucked the breast more. The mother-child interaction "infant self-stimulation-mother looks absent" and "Infant sucks the breast-mother looks absent" occurred more often during the mothers' traumatic narrations. The "absence" of the mother during trauma recall seems to have repercussions on infants' behavior and interaction; infants show coping strategies that are discussed. We found no significant associations between interaction and infant gender and age, the severity of traumatic experience, mothers' depression and anxiety symptoms, and the country of residence. The results of the microanalysis of interaction can shed light on the fundamental role of intermodal exchanges between mother and infant in trauma transmission during mothers' trauma reactivation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Dozio, Feldman, Bizouerne, Drain, Laroche Joubert, Mansouri, Moro and Ouss.)

Genoidentical HSCT is currently the only curative treatment for SCA, preventing further vascular complications in high-risk children. Studies on the psychological implications of HSCT for recipient, sibling donor, and the rest of the family have been limited in SCA. This study enrolled ten families and used semi-structured interviews to explore the parents' experience at three time points: first before transplantation, then 3 months later, and 1 year later. Three themes emerged from the results: (a) the presence of anxiety, experienced throughout the process, and alleviated by coping strategies (positive thinking, family support, praying); (b) the ability to remain parents to recipient and other family members, despite apprehension and feelings of helplessness, reinforced by the mobilization of important resources at the individual/family levels; (c) the ability to acknowledge the opportunity for their child to be cured of the disease, despite feelings of guilt toward families without a donor, or their own families back home. Overall, the parental experience with HSCT is complex, involving intra-psychic, familial, cultural, religious, and existential factors. Thus, it is important for medical teams to be cognizant of these issues in order to provide the best support to families during the HSCT process., (2019 Wiley Periodicals, Inc.)

Importance: In children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown., Objective: To determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA., Design, Setting, and Participants: Nonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor., Exposures: MSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching., Main Outcomes and Measures: The primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years., Results: Sixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, -40.8 cm/s [95% CI, -62.9 to -18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, -44.3 [95% CI, -71.9 to -21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, -1624 [95% CI, -2370 to -879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, -1788 [95% CI, -2570 to -1006]; P < .001)., Conclusions and Relevance: Among children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up., Trial Registration: ClinicalTrials.gov Identifier: NCT01340404.

This study explores the feasibility of using a combination of experimental and theoretical 1-bond 13 C─ 13 C scalar couplings ( 1 J CC ) to establish structure in organic compounds, including unknowns. Historically, n J CC and n J CH studies have emphasized 2 and 3-bond couplings, yet 1 J CC couplings exhibit significantly larger variations. Moreover, recent improvements in experimental measurement and data processing methods have made 1 J CC data more available. Herein, an approach is evaluated in which a collection of theoretical structures is created from a partial nuclear magnetic resonance structural characterization. Computed 1 J CC values are compared to experimental data to identify candidates giving the best agreement. This process requires knowledge of the error in theoretical methods, thus the B3LYP, B3PW91, and PBE0 functionals are evaluated by comparing to 27 experimental values from INADEQUATE. Respective errors of ±1.2, ±3.8, and ±2.3 Hz are observed. An initial test of this methodology involves the natural product 5-methylmellein. In this case, only a single candidate matches experimental data with high statistical confidence. This analysis establishes the intramolecular hydrogen-bonding arrangement, ring heteroatom identity, and conformation at one position. This approach is then extended to hydroheptelidic acid, a natural product not fully characterized in prior studies. The experimental/theoretical approach proposed herein identifies a single best-fit structure from among 26 candidates and establishes, for the first time, 1 configuration and 3 conformations to complete the characterization. These results suggest that accurate and complete structural characterizations of many moderately sized organic structures (<800 Da) may be possible using only 1 J CC data., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated., Design: DREPAGREFFE (NCT01340404) is a multicenter, prospective trial enrolling SCA children younger than 15years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥200cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost., Objectives: To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke., Discussion: DREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods., (Copyright © 2017. Published by Elsevier Inc.)