Functional characterization of 5’ UTR cis-acting sequence elements that modulate translational efficiency in P. falciparum and humans

The eukaryotic parasite Plasmodium falciparum causes millions of malarial infections annually and drug resistance to common antimalarials confounds eradication efforts. Protein translation is an attractive therapeutic target that will benefit from a deeper mechanistic understanding. Translation initiation drives translational efficiency and is regulated by both cis and trans acting factors. P. falciparum mRNAs feature unusual 5’ untranslated regions suggesting that cis-acting sequences could play a significant role in determining translational efficiency. Here, we deployed in vitro translation to compare the role of cis-acting regulatory sequences in P. falciparum and humans. Using parasite mRNAs with high or low translational efficiency, the presence, position, and termination status of upstream start site, in addition to the base composition of the 5’ untranslated regions, were characterized. Within 130 nucleotide 5’ untranslated regions, upstream start sites were generally repressive but exhibited a nonadditive effect when combined, while the base composition of the two mRNAs demonstrated a more subtle role in regulating translational efficacy. Surprisingly, the effects of cis-acting sequences were remarkably conserved between P. falciparum and humans. While translational regulation is inherently complex, this work contributes toward a more comprehensive understanding of parasite and human translational regulation by examining the impact of discreet cis-acting features.

Therapeutic Relationship and Dropout in High-Risk Adolescents’ Intensive Group Psychotherapeutic Programme

ObjectiveDropout rates are a prominent problem in youth psychotherapy. An important determinant of dropouts is the quality of the therapeutic relationship. This study aimed to evaluate the association between the therapeutic relationship and dropouts in an intensive mentalization-based treatment (MBT) for adolescents with personality disorders.MethodsPatients (N = 105) included were either dropouts (N = 36) or completers (N = 69) of an intensive MBT. The therapeutic relationship was measured with the child version of the Session Rating Scale (C-SRS), which was completed by the patient after each group therapy session. For each patient, the treatment termination status (dropout or completer) was indicated by the treatment staff. The reliable change index (RCI) was calculated for the C-SRS to determine significant changes in the therapeutic relationship.ResultsWhile both groups started with similar scores on the C-SRS, the scores between dropouts and completers differed significantly at the end of the treatment period. On average, during therapy, an increase was seen in the scores of completers, and a decrease was seen in the scores of dropouts. While dropouts could not be predicted based on the C-SRS scores, a significant decrease (RCI) in C-SRS scores during the last two sessions occurred more often for dropouts than for completers.ConclusionOur findings show that to prevent dropouts, the patient’s judgment of the quality of the therapeutic relationship should be monitored continuously, and decreases discussed with the patient and the group.

Second-trimester medication abortion outside the clinic setting: an analysis of electronic client records from a safe abortion hotline in Indonesia

IntroductionUnsafe abortion past the first trimester disproportionately accounts for the majority of global abortion-related morbidity and mortality; research that documents the safety, feasibility and acceptability of existing models for providing information and support to women who self-manage outside of formal clinic settings is needed.MethodsThis study is a retrospective analysis of anonymised electronic client records from callers to a safe abortion hotline in Indonesia. Between July 2012 and October 2016, a total of 96 women contacted the hotline for information on medication abortion beyond 12 weeks' gestation and are included in this study. Descriptive statistics were calculated regarding pregnancy termination status, client experience with warning signs of potential complications, and medical care seeking and treatment.ResultsNinety-six women with pregnancies beyond the first trimester called the hotline for information on medication abortion; 91 women received counselling support from the hotline. Eighty-three women (91.2%) successfully terminated their pregnancies using medication and did not seek medical care. Five women exhibited warning signs of potential complications and sought medical care; one woman sought care after a failed abortion. Two women were lost to follow-up and the outcomes of their pregnancies are unknown.ConclusionsEvidence from our analysis suggests that a model of remote provision of support for abortions later in pregnancy by non-medically trained, skilled abortion counsellors could be a safe alternative for women in need of abortions beyond 12 weeks' gestation in a legally restrictive context. Further examination and documentation of the model is warranted.