Structural Basis for the Interaction Between Yeast Chromatin Assembly Factor 1 and Proliferating Cell Nuclear Antigen.

Proliferating cell nuclear antigen (PCNA), the homotrimeric eukaryotic sliding clamp protein, recruits and coordinates the activities of a multitude of proteins that function on DNA at the replication fork. Chromatin assembly factor 1 (CAF-1), one such protein, is a histone chaperone that deposits histone proteins onto DNA immediately following replication. The interaction between CAF-1 and PCNA is essential for proper nucleosome assembly at silenced genomic regions. Most proteins that bind PCNA contain a PCNA-interacting peptide (PIP) motif, a conserved motif containing only eight amino acids. Precisely how PCNA is able to discriminate between binding partners at the replication fork using only these small motifs remains unclear. Yeast CAF-1 contains a PIP motif on its largest subunit, Cac1. We solved the crystal structure of the PIP motif of CAF-1 bound to PCNA using a new strategy to produce stoichiometric quantities of one PIP motif bound to each monomer of PCNA. The PIP motif of CAF-1 binds to the hydrophobic pocket on the front face of PCNA in a similar manner to most known PIP-PCNA interactions. However, several amino acids immediately flanking either side of the PIP motif bind the IDCL or C-terminus of PCNA, as observed for only a couple other known PIP-PCNA interactions. Furthermore, mutational analysis suggests positively charged amino acids in these flanking regions are responsible for the low micromolar affinity of CAF-1 for PCNA, whereas the presence of a negative charge upstream of the PIP prevents a more robust interaction with PCNA. These results provide additional evidence that positive charges within PIP-flanking regions of PCNA-interacting proteins are crucial for specificity and affinity of their recruitment to PCNA at the replication fork.

Assessing acceptability and effectiveness of a pleasure-oriented sexual and reproductive health chatbot in Kenya: an exploratory mixed-methods study.

Integrating pleasure may be a successful strategy for reaching young people with sexual and reproductive health and rights (SRHR) interventions. However, sexual pleasure-related programming and research remains sparse. We aimed to assess chatbot acceptability and describe changes in SRHR attitudes and behaviours among Kenyan young adults engaging with a pleasure-oriented SRHR chatbot. We used an exploratory mixed-methods study design. Between November 2021 and January 2022, participants completed a self-administered online questionnaire before and after chatbot engagement. In-depth phone interviews were conducted among a select group of participants after their initial chatbot engagement. Quantitative data were analysed using paired analyses and interviews were analysed using thematic content analysis. Of 301 baseline participants, 38% (115/301) completed the endline survey, with no measured baseline differences between participants who did and did not complete the endline survey. In-depth interviews were conducted among 41 participants. We observed higher satisfaction at endline vs. baseline on reported ability to exercise sexual rights (P ≤ 0.01), confidence discussing contraception (P ≤ 0.02) and sexual feelings/needs (P ≤ 0.001) with their sexual partner(s). Qualitative interviews indicated that most participants valued the chatbot as a confidential and free-of-judgment source of trustworthy "on-demand" SRHR information. Participants reported improvements in sex-positive communication with partners and safer sex practices due to new learnings from the chatbot. We observed increases in SRHR empowerment among young Kenyans after engagement with the chatbot. Integrating sexual pleasure into traditional SRHR content delivered through digital tools is a promising strategy to advance positive SRHR attitudes and practices among youth.

Introducing the hormonal Intrauterine Device in Madagascar, Nigeria, and Zambia: results from a pilot study.

BACKGROUND: The hormonal Intrauterine Device (IUD) is a highly effective contraceptive option growing in popularity and availability in many countries. The hormonal IUD has been shown to have high rates of satisfaction and continuation among users in high-income countries. The study aims to understand the profiles of clients who choose the hormonal IUD in low- and middle-income countries (LMICs) and describe their continuation and satisfaction with the method after 12 months of use. METHODS: A prospective longitudinal study of hormonal IUD acceptors was conducted across three countries-Madagascar, Nigeria, and Zambia-where the hormonal IUD had been introduced in a pilot setting within the of a broad mix of available methods. Women were interviewed at baseline immediately following their voluntary hormonal IUD insertion, and again 3 and 12 months following provision of the method. A descriptive analysis of user characteristics and satisfaction with the method was conducted on an analytic sample of women who completed baseline, 3-month, and 12-month follow-up questionnaires. Kaplan-Meier time-to-event models were used to estimate the cumulative probability of method continuation rates up to 12 months post-insertion. RESULTS: Each country had a unique demographic profile of hormonal IUD users with different method-use histories. Across all three countries, women reported high rates of satisfaction with the hormonal IUD (67-100%) and high rates of continuation at the 12-month mark (82-90%). CONCLUSIONS: Rates of satisfaction and continuation among hormonal IUD users in the study suggest that expanding method choice with the hormonal IUD would provide a highly effective, long-acting method desirable to many different population segments, including those with high unmet need.

Supporting contraceptive choice in self-care: qualitative exploration of beliefs and attitudes towards emergency contraceptive pills and on-demand use in Accra, Ghana and Lusaka, Zambia.

Supporting women to use emergency contraceptive pills (ECPs) as both a back-up and a regular, on-demand contraceptive method can increase self-managed contraceptive options and enhance reproductive autonomy, particularly for vulnerable populations. ECPs are currently regulated for use in an "emergency" situation; however, some evidence suggests that women also value this method as a regular, on-demand option used to prevent pregnancy with foresight and confidence. Beliefs and attitudes towards ECPs and their on-demand use in Accra, Ghana and Lusaka, Zambia were explored through in-depth interviews (IDIs) and focus group discussions (FGDs) with women ages 18-34 and men ages 18-30 in Accra and Lusaka. Structured interview guides and focus group discussion guides were used to explore societal and community norms, knowledge, behaviour, and attitudes. IDIs were analysed using deductive, thematic coding, and FGDs were analysed using inductive, thematic coding. Three major themes emerged: first, ECPs are a trusted method and often preferred as an easy and effective option; second, people value ECPs as an on-demand method, yet fear that repeated use could have harmful health effects; finally, anticipated stigma among users of ECPs is higher than experienced stigma, except among young women. The findings that emerged from this research suggest that the repositioning of ECPs as suitable for on-demand use would be an important step towards reducing the stigma and discrimination that is often associated with the method while expanding the range of self-care contraceptive options available to meet the differing needs of women, young women and vulnerable populations.

Quality healthcare in extreme adversity: Developing a framework for action.

Quality issue: Improving quality of care has become a global health priority to improve health outcomes and strengthen health systems, particularly in the context of achieving universal health coverage. Initial assessment: The delivery of quality essential health services in settings of extreme adversity, such as fragile, conflict-affected, vulnerable or disaster contexts, has been identified as a high priority globally to address the massive level of need. Choice of solution: This paper provides an action framework to systematically address the quality of health services for state and non-state actors working in such settings. The framework is designed to be practical, comprehensible and simple in adoption and implementation. It describes challenges, a set of medical needs and population priorities, a menu of quality-related interventions, and a hierarchy of health system levels defining the roles and responsibilities of key actors. Conclusion: Optimizing the use of limited resources in delivering the best quality possible in 'the hardest of the hard settings' is imperative.

Quality health care in extreme adversity-an action framework.

QUALITY PROBLEM OR ISSUE: There are record-setting numbers of people living in settings of extreme adversity and they continue to increase each year. INITIAL ASSESSMENT: There is a paucity of validated data on quality and safety across settings of extreme adversity. CHOICE OF SOLUTION: This paper argues for an action framework to address the unique challenges of providing quality in extreme adversity. IMPLEMENTATION: We describe a preliminary Quality in Extreme Adversity framework which has been informed by-and will continue to be validated through-literature, data collection, WHO expert consultations and through working in settings of extreme adversity with national authorities and NGOs. LESSONS LEARNED: Poor quality care costs lives, livelihoods and trust in health services. The recommended framework, based on evidence and experiential lessons, intends to address the WHO goal for 2019-2023 of 'one billion people better protected from health emergencies' (9).