Comparative analyses of the Smith-Magenis syndrome protein RAI1 in mice and common marmoset monkeys.

Retinoic acid-induced 1 (RAI1) encodes a transcriptional regulator critical for brain development and function. RAI1 haploinsufficiency in humans causes a syndromic autism spectrum disorder known as Smith-Magenis syndrome (SMS). The neuroanatomical distribution of RAI1 has not been quantitatively analyzed during the development of the prefrontal cortex, a brain region critical for cognitive function and social behaviors and commonly implicated in autism spectrum disorders, including SMS. Here, we performed comparative analyses to uncover the evolutionarily convergent and divergent expression profiles of RAI1 in major cell types during prefrontal cortex maturation in common marmoset monkeys (Callithrix jacchus) and mice (Mus musculus). We found that while RAI1 in both species is enriched in neurons, the percentage of excitatory neurons that express RAI1 is higher in newborn mice than in newborn marmosets. By contrast, RAI1 shows similar neural distribution in adult marmosets and adult mice. In marmosets, RAI1 is expressed in several primate-specific cell types, including intralaminar astrocytes and MEIS2-expressing prefrontal GABAergic neurons. At the molecular level, we discovered that RAI1 forms a protein complex with transcription factor 20 (TCF20), PHD finger protein 14 (PHF14), and high mobility group 20A (HMG20A) in the marmoset brain. In vitro assays in human cells revealed that TCF20 regulates RAI1 protein abundance. This work demonstrates that RAI1 expression and protein interactions are largely conserved but with some unique expression in primate-specific cells. The results also suggest that altered RAI1 abundance could contribute to disease features in disorders caused by TCF20 dosage imbalance.

Use of an electronic Partograph: feasibility and acceptability study in Zanzibar, Tanzania.

BACKGROUND: The ePartogram is a tablet-based application developed to improve care for women in labor by addressing documented challenges in partograph use. The application is designed to provide real-time decision support, improve data entry, and increase access to information for appropriate labor management. This study's primary objective was to evaluate the feasibility and acceptability of ePartogram use in resource-constrained clinical settings. METHODS: The ePartogram was introduced at three facilities in Zanzibar, Tanzania. Following 3 days of training, skilled birth attendants (SBAs) were observed for 2 weeks using the ePartogram to monitor laboring women. During each observed shift, data collectors used a structured observation form to document SBA comfort, confidence, and ability to use the ePartogram. Results were analyzed by shift. Short interviews, conducted with SBAs (n = 82) after each of their first five ePartogram-monitored labors, detected differences over time. After the observation period, in-depth interviews were conducted (n = 15). A thematic analysis of interview transcripts was completed. RESULTS: Observations of 23 SBAs using the ePartogram to monitor 103 women over 84 shifts showed that the majority of SBAs (87-91%) completed each of four fundamental ePartogram tasks-registering a client, entering first and subsequent measurements, and navigating between screens-with ease or increasing ease on their first shift; this increased to 100% by the fifth shift. Nearly all SBAs (93%) demonstrated confidence and all SBAs demonstrated comfort in using the ePartogram by the fifth shift. SBAs expressed positive impressions of the ePartogram and found it efficient and easy to use, beginning with first client use. SBAs noted the helpfulness of auditory reminders (indicating that measurements were due) and visual alerts (signaling abnormal measurements). SBAs expressed confidence in their ability to interpret and act on these reminders and alerts. CONCLUSIONS: It is feasible and acceptable for SBAs to use the ePartogram to support labor management and care. With structured training and support during initial use, SBAs quickly became competent and confident in ePartogram use. Qualitative findings revealed that SBAs felt the ePartogram improved timeliness of care and supported decision-making. These findings point to the ePartogram's potential to improve quality of care in resource-constrained labor and delivery settings.

Placental malaria is rare among Zanzibari pregnant women who did not receive intermittent preventive treatment in pregnancy.

Zanzibar has transitioned from malaria control to the pre-elimination phase, and the continued need for intermittent preventive treatment during pregnancy (IPTp) has been questioned. We conducted a prospective observational study to estimate placental malaria positivity rate among women who did not receive IPTp with sulfadoxine-pyrimethamine. A convenience sample of pregnant women was enrolled from six clinics on the day of delivery from August of 2011 to September of 2012. Dried placental blood spot specimens were analyzed by polymerase chain reaction (PCR); 9 of 1,349 specimens (0.7%; precision estimate = 0.2-1.1%) were PCR-positive for Plasmodium falciparum. Placental infection was detected on both Pemba (N = 3) and Unguja (N = 6). Placental malaria positivity in Zanzibar was low, even in the absence of IPTp. It may be reasonable for the Ministry of Health to consider discontinuing IPTp, intensifying surveillance efforts, and promoting insecticide-treated nets and effective case management of malaria in pregnancy.

Competency-based training "Helping Mothers Survive: Bleeding after Birth" for providers from central and remote facilities in three countries.

OBJECTIVE: To validate a new training module for skilled and semiskilled birth attendants authorized to provide care at birth-Helping Mothers Survive: Bleeding After Birth (HMS:BAB)-aimed at reducing postpartum hemorrhage, the leading cause of maternal mortality worldwide. BAB training involves single-day, facility-based training that emphasizes simulation of scenarios related to prevention, detection, and management of postpartum hemorrhage. METHODS: A total of 155 skilled and semiskilled birth attendants participated in training in India, Malawi, and Zanzibar, Tanzania. Knowledge and confidence were assessed before and after training. Skills and acceptability were assessed after training. RESULTS: Knowledge and confidence scores improved significantly from pre- to post-training among all cadres in all three countries. The proportion of providers with passing knowledge scores increased significantly from pre- to post-training among all cadres except for those already high at baseline. On three post-training skills tests the overall proportion of individuals with a passing score ranged from 83% to 89%. CONCLUSION: BAB training in prevention and management of postpartum hemorrhage increased knowledge and confidence among skilled and semiskilled birth attendants. Further studies are needed to determine the impact of this training on skills retention and clinical outcomes following postpartum hemorrhage, after broader implementation of the training program.