Pioneering the developmental frontier.

Coordinated changes in gene expression allow a single fertilized oocyte to develop into a complex multi-cellular organism. These changes in expression are controlled by transcription factors that gain access to discrete cis-regulatory elements in the genome, allowing them to activate gene expression. Although nucleosomes present barriers to transcription factor occupancy, pioneer transcription factors have unique properties that allow them to bind DNA in the context of nucleosomes, define cis-regulatory elements, and facilitate the subsequent binding of additional factors that determine gene expression. In this capacity, pioneer factors act at the top of gene-regulatory networks to control developmental transitions. Developmental context also influences pioneer factor binding and activity. Here we discuss the interplay between pioneer factors and development, their role in driving developmental transitions, and the influence of the cellular environment on pioneer factor binding and activity.

Care-seeking for difficulties conceiving in sub-Saharan Africa: findings from population-based surveys in eight geographies.

STUDY QUESTION: What is the nature of women's care-seeking for difficulties conceiving in sub-Saharan Africa (SSA), including the correlates of seeking biomedical infertility care at a health facility? SUMMARY ANSWER: Care-seeking for difficulties getting pregnant was low, much of which involved traditional or religious sources of care, with evidence of sociodemographic disparities in receipt of biomedical care. WHAT IS KNOWN ALREADY: Nearly all research on infertility care-seeking patterns in SSA is limited to clinic-based studies among the minority of people in these settings who obtain facility-based services. In the absence of population-based data on infertility care-seeking, we are unable to determine the demand for services and disparities in the use of more effective biomedical sources of care. STUDY DESIGN, SIZE, DURATION: We used cross-sectional, population-based data from the Performance Monitoring for Action (PMA) female survey in eight geographies in SSA, including nationally representative data from Burkina Faso, Côte d'Ivoire, Kenya, and Uganda and regionally representative data from two provinces in the Democratic Republic of the Congo (DRC) (Kinshasa and Kongo Central) and two states in Nigeria (Kano and Lagos). We employed a multi-stage cluster random sampling design with probability proportional to size selection of clusters within each geography to produce representative samples of women aged 15-49. Samples ranged from 1144 in Kano, Nigeria, to 9489 in Kenya. PMA collected these data between November 2021 and December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: We restricted the sample to women who had ever had sex, with analytic samples ranging from 854 in Kano to 8,059 in Kenya, then conducted descriptive and bivariable analyses to examine characteristics of those who sought care for difficulties getting pregnant. Among those who reported seeking care, we conducted bivariable and multivariable logistic regression analyses to determine factors associated with receipt of biomedical services from a health facility. All analyses were conducted separately by geography. MAIN RESULTS AND THE ROLE OF CHANCE: Our study found low levels of care-seeking for difficulties getting pregnant among sexually active women in eight geographies in SSA, ranging from 3.7% (Kenya) to 15.3% (Côte d'Ivoire). Of this, 51.8% (Burkina Faso) to 86.7% (Kinshasa) involved receipt of biomedical services in health facilities. While many factors were consistently associated with infertility care-seeking from any source across geographies, factors associated with receipt of biomedical care specifically were less pronounced. This may be a result of the highly limited sources of infertility services in SSA; thus, even privileged groups may struggle to obtain effective treatment for difficulties getting pregnant. However, we did observe disparities in biomedical care-seeking in our bivariable results in several geographies, with the wealthiest women, those with more education, and those residing in urban areas generally more likely to have sought biomedical care for difficulties getting pregnant. LIMITATIONS, REASONS FOR CAUTION: Our data lacked details on the nature of the services received and outcomes, and we do not have information on reasons why women chose the sources they did. Small samples of women who sought care limited our power to detect significant differences in care-seeking by women's characteristics in several geographies. WIDER IMPLICATIONS OF THE FINDINGS: Infertility and access to appropriate treatment are issues of reproductive health and human rights. While our results do not indicate to what extent use of non-biomedical sources of care is driven by preferences, cost, or lack of accessible services, it is clear from our results and existing literature that more needs to be done to ensure access to affordable, quality, cost-effective infertility services in SSA. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Bill & Melinda Gates Foundation (INV009639) and the National Institute of Child Health and Human Development (K01HD107172). The funders were not involved in the study design, analyses, manuscript writing, or the decision to publish. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Reconceptualizing Measurement of Emergency Contraceptive Use: Comparison of Approaches to Estimate the Use of Emergency Contraception.

Estimated use of emergency contraception (EC) remains low, and one reason is measurement challenges. The study aims to compare EC use estimates using five approaches. Data come from Performance Monitoring and Accountability 2020 surveys from 10 countries, representative sample surveys of women aged 15 to 49 years. We explore EC use employing the five definitions and calculate absolute differences between a reference definition (percentage of women currently using EC as the most effective method) and each of the subsequent four, including the most inclusive (percentage of women having used EC in the past year). Across the 17 geographies, estimated use varies greatly by definition and EC use employing the most inclusive definition is statistically significantly higher than the reference estimate. Impact of using various definitions is most pronounced among unmarried sexually active women. The conventional definition of EC use likely underestimates the magnitude of EC use, which has unique programmatic implications.

Does a Sway-Based Mobile Application Predict Future Falls in People With Parkinson Disease?

OBJECTIVE: To determine whether Sway, a sway-based mobile application, predicts falls and to evaluate its discriminatory sensitivity and specificity relative to other clinical measures in identifying fallers in individuals with Parkinson disease (PD). DESIGN: Observational cross-sectional study. SETTING: Community. PARTICIPANTS: A convenience sample of subjects with idiopathic PD in Hoehn and Yahr levels I-III (N=59). INTERVENTIONS: Participants completed a balance assessment using Sway, the Movement Disorders Systems-Unified PD Rating Scale motor examination, Mini-BESTest, Activities-specific Balance Confidence (ABC) Scale, and reported 6-month fall history. Participants also reported falls for each of the following 6 months. Binomial logistic regression was used to identify significant predictors of future fall status. Cutoff scores, sensitivity, and specificity were based on receiver operating characteristic plots. MAIN OUTCOME MEASURES: Sway score. RESULTS: The most predictive logistic regression model included fall history, ABC Scale, and Sway (P<.001). This model explained 61% (Nagelkerke R2) of the variance in fall prediction and correctly classified 85% of fallers. However, only fall history and ABC Scale were statistically significant (P<.02). Participants were 32 times more likely to fall in the future if they fell in the past. The ABC Scale and Mini Balance Evaluation Systems Test (Mini-BESTest) demonstrated greater accuracy than Sway (area under the curve=0.76, 0.72, and 0.65, respectively). Cutoff scores to identify fallers were 85% for the ABC Scale and 21 of 28 for the Mini-BESTest. CONCLUSION: Sway did not improve the accuracy of predicting future fallers beyond common clinical measures and fall history.

A conserved maternal-specific repressive domain in Zelda revealed by Cas9-mediated mutagenesis in Drosophila melanogaster.

In nearly all metazoans, the earliest stages of development are controlled by maternally deposited mRNAs and proteins. The zygotic genome becomes transcriptionally active hours after fertilization. Transcriptional activation during this maternal-to-zygotic transition (MZT) is tightly coordinated with the degradation of maternally provided mRNAs. In Drosophila melanogaster, the transcription factor Zelda plays an essential role in widespread activation of the zygotic genome. While Zelda expression is required both maternally and zygotically, the mechanisms by which it functions to remodel the embryonic genome and prepare the embryo for development remain unclear. Using Cas9-mediated genome editing to generate targeted mutations in the endogenous zelda locus, we determined the functional relevance of protein domains conserved amongst Zelda orthologs. We showed that neither a conserved N-terminal zinc finger nor an acidic patch were required for activity. Similarly, a previously identified splice isoform of zelda is dispensable for viability. By contrast, we identified a highly conserved zinc-finger domain that is essential for the maternal, but not zygotic functions of Zelda. Animals homozygous for mutations in this domain survived to adulthood, but embryos inheriting these loss-of-function alleles from their mothers died late in embryogenesis. These mutations did not interfere with the capacity of Zelda to activate transcription in cell culture. Unexpectedly, these mutations generated a hyperactive form of the protein and enhanced Zelda-dependent gene expression. These data have defined a protein domain critical for controlling Zelda activity during the MZT, but dispensable for its roles later in development, for the first time separating the maternal and zygotic requirements for Zelda. This demonstrates that highly regulated levels of Zelda activity are required for establishing the developmental program during the MZT. We propose that tightly regulated gene expression is essential to navigate the MZT and that failure to precisely execute this developmental program leads to embryonic lethality.

"I Knew I Could Make a Difference": Motivations and Barriers to Engagement in Fighting the West African Ebola Outbreak Among U.S.-Based Health Professionals.

The 2014 West African Ebola outbreak was unprecedented in scale and required significant international assistance. Many U.S.-based health professionals traveled to West Africa to participate in the response, whereas others considered participation, but ultimately decided against it. This study explores motivators, facilitators, and barriers to international health care worker mobilization. We conducted 24 semistructured in-depth interviews and one focus group discussion with clinical and nonclinical responders and nonresponders. Responders reported feeling duty-bound to help, confidence in their training, and prior experience in humanitarian response. Media coverage was perceived to create environments of stigma and misinformation. Supportive workplaces and clear leave of absence policies facilitated engagement, whereas unsupportive workplaces posed barriers. Although nonresponders were included in the study, the dynamics of nonresponse were less clear and warrant further exploration. Understanding how to support health professionals in responding to outbreak situations may improve mobilization in future public health crises.

5Minutes4Myself: Development of a Wellness Program for Caregivers of Children with Autism.

Background. Many caregivers of autistic children experience increased stress, and diminished health often due to the caregiving demands. Purpose. The project aim was to design a feasible and sustainable wellness program tailored to these caregivers' lives. Methods. In this collaborative research-informed project, participants (N = 28) were mostly female, white, and well-educated. In focus groups, we delineated lifestyle issues, then designed, delivered and assessed an initial program with one cohort; and repeated this process with a second group. Findings. Focus group data were transcribed then coded qualitatively to inform following steps. Data analysis identified lifestyle issues key to program design, desired program elements, and after program delivery, affirmed elements and recommended changes. The team used meta-inferences to guide program revisions after each cohort. Implications. Caregivers viewed resulting 5Minutes4Myself program as filling a significant service gap; its hybrid design used in-person coaching and a habit-building app with mindfulness content to support lifestyle change.

Protein-intrinsic properties and context-dependent effects regulate pioneer factor binding and function.

Chromatin is a barrier to the binding of many transcription factors. By contrast, pioneer factors access nucleosomal targets and promote chromatin opening. Despite binding to target motifs in closed chromatin, many pioneer factors display cell-type-specific binding and activity. The mechanisms governing pioneer factor occupancy and the relationship between chromatin occupancy and opening remain unclear. We studied three Drosophila transcription factors with distinct DNA-binding domains and biological functions: Zelda, Grainy head and Twist. We demonstrated that the level of chromatin occupancy is a key determinant of pioneering activity. Multiple factors regulate occupancy, including motif content, local chromatin and protein concentration. Regions outside the DNA-binding domain are required for binding and chromatin opening. Our results show that pioneering activity is not a binary feature intrinsic to a protein but occurs on a spectrum and is regulated by a variety of protein-intrinsic and cell-type-specific features.

Balancing the uncertain and unpredictable nature of possible zoonotic disease transmission with the value placed on animals: Findings from a qualitative study in Guinea.

Zoonoses, or diseases that pass between animals and humans, represent a major threat to global health and global economies. In Guinea, zoonotic diseases (e.g. rabies, Lassa fever) have been at the forefront due to recent outbreaks and government priorities. Much like many other diseases, zoonotic disease prevention demands a thorough and culturally nuanced understanding of the factors that influence preventive behaviors. To gain this knowledge and enhance risk communication for priority zoonotic diseases, this qualitative study conducted focus group discussions, in-depth interviews, and observations in three Guinean prefectures. Study participants included individuals who interact with animals or influence human-animal interactions, (e.g., veterinarians, local leaders, human health providers, butchers, hunters, general population). A total of 229 individuals participated in the study. Data analysis, which combined deductive and inductive coding, found that although individuals generally had basic knowledge about zoonotic diseases, a gap existed between knowledge and practice. In exploring possible reasons behind this gap, several key themes arose, the two most novel being the focus of this paper. First, participants described living in an uncertain world where they lack control over the behaviors of others. Many participants described uncertainty over the vaccine status of stray dogs or even those of their neighbors, making them feel powerless over rabies. Second, animals serve as a main source of livelihood (income, investment, or savings) for individuals. The value placed on livestock may, in turn, drive and impede prevention behaviors such as vaccinating animals or avoiding the sale of unsafe meat. Given that the Guinean government's list of priority zoonotic diseases continues to evolve, the need to discover ways to effectively promote multiple related prevention behaviors remains pertinent. The insights from this study can inform existing and future programs for the prevention, control, and surveillance of zoonotic disease in Guinea and other similar countries.

Mixed-method evaluation of fidelity of motivational interviewing-based coaching in 5Minutes4Myself Wellness Program for caregivers of children with autism.

Objective: This mixed method analysis examined fidelity of the motivational interviewing (MI) delivered during the 5Minutes4Myself wellness program for caregivers of children with Autism Spectrum Disorders. Methods: Coaches used a manualized MI-approach to collaboratively design participants' individualized wellness programs, and then used it in monthly coaching sessions to support goal pursuit. Audio-recorded consultations and post-participation focus groups were transcribed verbatim. Consultation transcripts were rated for MI adherence using Motivational Interviewing Treatment Integrity Code. Focus group data was coded by the team to identify conceptual categories. Results: Eighty-seven percent of consultations achieved a beginning (competent) level expert-derived MI standard. Caregivers noted that coaches' MI approach evoked deep emotions and understandings about their lives related to wellness goals, allowed for a permissive flexibility in goal pursuit, and fostered supportive accountability. Conclusion: MI was used with high levels of fidelity. Participants described the MI approach as more productive, precise, and useful in addressing their needs compared to other available interventions.

Abortion incidence and safety in Niger in 2021: Findings from a nationally representative cross-sectional survey of reproductive-aged women using direct and indirect measurement approaches.

Niger is a country in which legal restrictions and a dearth of research has long limited our understanding of the extent and safety of induced abortion. The current study is the first national study of induced abortion in Niger. It uses direct (self-report) and indirect (best friend method) to provide nationally representative estimates of induced abortion incidence and safety and evaluates the performance of the indirect measurement approach. We used cross-sectional, representative survey data on women aged 15-49 in Niger collected between January and May 2022; final sample included 3,696 women. The survey included questions on respondents' and their closest female friends' experience with abortion, including methods and sources used. We calculated one-year abortion incidence and the proportion of abortions involving non-recommended methods and/or sources to determine safety separately for respondents and friends, overall and by background characteristics. The fully adjusted one-year friend abortion rate was 6.7 abortions per 1,000 women in 2021, which was substantially higher than the corresponding respondent rate of 0.4 per 1,000 women. Confidence intervals were wide, but friend estimates suggest higher abortion rates among women in their 20s, those with secondary or higher education, and those with no children. Nearly all abortions were unsafe (97% respondents, 100% friends), involving non-recommended methods and/or sources. While abortion numbers were small, unsafe abortion appeared more common among older women, married women, those with children, and those residing in rural areas. Our findings indicate that, despite legal restrictions, some women undergo abortions in Niger at great risk to their physical safety. Ensuring adequate access to quality voluntary family planning services to prevent unintended pregnancy and postabortion care to treat complications is essential to reducing the risk of unsafe abortion in the country.

Putting our money where our mouth is? The degree of women-centred family planning in the era of FP2020.

The 1994 International Conference on Population and Development was a landmark moment for the international family planning community, who committed to adopt a women-centred approach to programming-one that would prioritise the reproductive and contraceptive intentions, or autonomy, of individuals over population-level demographic concerns. The FP2020 partnership, established in 2012 and lasting until 2020, also described itself using women-centred language. However, throughout the period of FP2020, critics questioned the extent to which women-centred principles truly defined why family planning programmes were funded and how they were implemented. In this study, we use thematic discourse analysis to examine six major international donors' rationale(s) for funding family planning and the measurements they used to articulate successful programming. We present an overview of the rationales and measurements used by all six donors before offering four case studies to demonstrate divergences in their approaches. Our analysis demonstrates that, although donors described the importance of family planning for fostering women's autonomy and empowerment, they also justified family planning on the basis of demographic concerns. In addition, we identified a misalignment between how donors described family planning programmes-using the language of voluntarism and choice-and how they measured their success-through increased uptake and use of contraceptive methods. We call on the international family planning community to reflect on their true motives for funding and implementing family planning and engage in radically rethinking how they capture programme success, in order to better align their rhetoric with their practice.

Estimating induced abortion incidence and the use of non-recommended abortion methods and sources in two provinces of the Democratic Republic of the Congo (Kinshasa and Kongo Central) in 2021: results from population-based, cross-sectional surveys of reproductive-aged women.

The changing abortion legal and practice landscape in the DRC in recent years calls for a re-examining of induced abortion experiences. The current study provides population-level estimates of induced abortion incidence and safety by women's characteristics in two provinces using direct and indirect approaches to assess indirect method performance. We use representative survey data on women aged 15-49 in Kinshasa and Kongo Central collected from December 2021 to April 2022. The survey had questions on respondents' and their closest friends' experience with induced abortion, including methods and sources used. We estimated one-year abortion incidence and proportion using non-recommended methods and sources overall and by background characteristics for each province separately for respondents and friends. The fully adjusted one-year friend abortion rate was 105.3 per 1000 women of reproductive age in Kinshasa and 44.3 per 1000 in Kongo Central in 2021; these were substantially higher than corresponding respondent estimates. Women earlier in their reproductive lifespan were more likely to have had a recent abortion. Approximately 17.0% of abortions in Kinshasa and one-third of abortions in Kongo Central involved non-recommended methods and sources according to respondent and friend estimates. The more accurate friend abortion incidence estimates indicate that women in the DRC often rely on abortion to regulate their fertility. Many use non-recommended means and sources to terminate, thus, significant work remains to actualise the commitments made in the Maputo Protocol to provide comprehensive reproductive health services that combine primary and secondary prevention services to reduce unsafe abortion and its consequences.

Low-level repressive histone marks fine-tune gene transcription in neural stem cells.

Coordinated regulation of gene activity by transcriptional and translational mechanisms poise stem cells for a timely cell-state transition during differentiation. Although important for all stemness-to-differentiation transitions, mechanistic understanding of the fine-tuning of gene transcription is lacking due to the compensatory effect of translational control. We used intermediate neural progenitor (INP) identity commitment to define the mechanisms that fine-tune stemness gene transcription in fly neural stem cells (neuroblasts). We demonstrate that the transcription factor FruitlessC (FruC) binds cis-regulatory elements of most genes uniquely transcribed in neuroblasts. Loss of fruC function alone has no effect on INP commitment but drives INP dedifferentiation when translational control is reduced. FruC negatively regulates gene expression by promoting low-level enrichment of the repressive histone mark H3K27me3 in gene cis-regulatory regions. Identical to fruC loss-of-function, reducing Polycomb Repressive Complex 2 activity increases stemness gene activity. We propose low-level H3K27me3 enrichment fine-tunes gene transcription in stem cells, a mechanism likely conserved from flies to humans.

From neurons to sperm, our bodies are formed of a range of cells tailored to perform a unique role. However, organisms also host small reservoirs of unspecialized 'stem cells' that retain the ability to become different kinds of cells. When these stem cells divide, one daughter cell remains a stem cell while the other undergoes a series of changes that allows it to mature into a specific cell type. This 'differentiation' process involves quickly switching off the stem cell programme, the set of genes that give a cell the ability to keep dividing while maintaining an unspecialized state. Failure to do so can result in the differentiating cell reverting towards its initial state and multiplying uncontrollably, which can lead to tumours and other health problems. While scientists have a good understanding of how the stem cell programme is turned off during differentiation, controlling these genes is a balancing act that starts even before division: if the program is over-active in the 'mother' stem cell, for instance, the systems that switch it off in its daughter can become overwhelmed. The mechanisms presiding over these steps are less well-understood. To address this knowledge gap, Rajan, Anhezini et al. set out to determine how stem cells present in the brains of fruit flies could control the level of activity of their own stem cell programme. RNA sequencing and other genetic analyses revealed that a protein unique to these cells, called Fruitless, was responsible for decreasing the activity of the programme. Biochemical experiments then showed that Fruitless performed this role by attaching a small amount of chemical modifications (called methyl groups) to the proteins that 'package' the DNA near genes involved in the stem cell programme. High levels of methyl groups present near a gene will switch off this sequence completely; however, the amount of methyl groups that Fruitless helped to deposit is multiple folds lower. Consequently, Fruitless 'fine-tunes' the activity of the stem cell programme instead, dampening it just enough to stop it from overpowering the 'off' mechanism that would take place later in the daughter cell. These results shed new light on how stem cells behave ­ and how our bodies stop them from proliferating uncontrollably. In the future, Rajan, Anhezini et al. hope that this work will help to understand and treat diseases caused by defective stem cell differentiation.

Sex and age differences in depression and baseline sport-related concussion neurocognitive performance and symptoms.

OBJECTIVE: To examine depression and baseline neurocognitive function and concussion symptoms in male and female high school and college athletes. DESIGN: Cross sectional. SETTING: Athletes completed testing at a designated computer laboratory at high schools and colleges. PARTICIPANTS: Participants included 1616 collegiate (n = 837) and high school (n = 779) athletes from 3 states participating in a variety of competitive sports. INTERVENTIONS: Participants completed the baseline Immediate Postconcussion Assessment and Cognitive Test (ImPACT), symptom inventory, and Beck Depression Inventory II (BDI-II). MAIN OUTCOME MEASURES: Between-group comparisons for depression groups on ImPACT composite scores (verbal and visual memory, reaction time, motor processing speed), total symptoms, and symptom cluster (sleep, cognitive, emotional, somatic/migraine) scores. Between-group comparisons for age and sex on BDI-II, ImPACT, total symptoms, and symptom cluster scores. RESULTS: The severe depression group scored worse on visual memory and reported more total, somatic/migraine, cognitive, emotional, and sleep symptoms than less depressed groups. High school athletes reported more somatic/migraine symptoms than collegiate athletes, whereas collegiate athletes reported more emotional and sleep symptoms than high school athletes. Women had higher verbal memory and reported more cognitive, emotional, and sleep symptom clusters compared with men. Women outperformed men on verbal memory, whereas collegiate athletes outperformed high school athletes on processing speed. CONCLUSIONS: Athletes with severe depression scored lower on visual memory than those with minimal depression. Athletes with severe depression report more concussion symptoms than athletes with minimal and moderate depression scores. Symptoms of depression should be included in baseline assessments to help disentangle depression from concussion symptoms.

Let's Talk About Sex: Improving Measurement of Contraceptive Use in Cross-Sectional Surveys by Accounting for Sexual Activity Recency.

INTRODUCTION: Standard measures of contraceptive prevalence have known biases given that they do not reflect sexual activity and true exposure to the risk of an unintended pregnancy. In this study, we aim to understand the extent to which women protect themselves against unintended pregnancy, taking into account exposure to sex, by examining contraceptive use patterns by marital status and recent sexual activity. METHODS: Data come from population-based surveys of reproductive age women in 9 low-resource settings. We estimated contraceptive prevalence using (1) the standard current contraceptive use measure, (2) a new measure of contraceptive use at last sex, and (3) a comprehensive measure that combines current use and use at last sex. Analyses are stratified by site and examine patterns by marital status only, and by both marital status and sexual activity separately. We then examined method mix by each contraceptive measure. RESULTS: Study findings reveal distinct patterns in contraceptive use in relation to marital status and sexual recency across sites. Overall, married women tended to report higher levels of current contraceptive use compared to use at last sex, whereas unmarried women reported higher levels of contraceptive use at last sex. When examining these measures by sexual activity and marital status, results indicate lower levels of contraceptive use among women who had not had sex in the month prior to the survey, for both married and unmarried women. The comprehensive measure of contraceptive use yielded the highest estimates, by design. Method mix varied consistently by contraceptive measure, with current use tending to capture more permanent and long-acting methods and use at last sex more likely to capture short-acting and coital-dependent methods. DISCUSSION: These findings have important implications for how the family planning field evaluates unintended pregnancy risk and unmet need for contraception within low-resource settings, given different estimates yield discrepant estimates for who is "at risk."

Physical Medicine and Rehabilitation Consultation for Stroke Patients in Acute Care Setting May Be Associated With an Increased Rate of Discharge to the Community From the Inpatient Rehabilitation Facility.

OBJECTIVE: The aim of the study was to determine whether stroke patients who receive physical medicine and rehabilitation consultation in acute care setting are more likely to discharge from inpatient rehabilitation facility to a community setting compared with those who do not. DESIGN: This was a retrospective analysis of consecutive patients admitted with stroke to inpatient rehabilitation facility between June and October 2018. The primary outcome measure was discharge disposition. Other variables measured included functional independence measures and length of stay. Analysis of baseline covariates was conducted with t tests and analysis of primary outcome measured with Fisher exact test. RESULTS: We identified 184 consecutive patients, with 62 (33.7%) having and 122 (66.3%) not having a physical medicine and rehabilitation consult; 35 (56.5%) patients versus 51 (41.8%) in physical medicine and rehabilitation consult versus non-physical medicine and rehabilitation group were discharged home (P = 0.042). Between both groups, there were no differences in baseline admission/discharge cognitive or motor functional independence measure scores, total admission/discharge functional independence measure scores, functional independence measure efficiency, or length of stay. However, in both the groups, admission versus discharge overall functional independence measure scores were significantly improved, 71.34 vs. 94.76 and 66.52 vs. 89.94 (P < 0.0001). CONCLUSIONS: Despite no difference in baseline functional scores or length of stay, physical medicine and rehabilitation consultation of poststroke patients in hospital may be associated with discharge home after inpatient rehabilitation facility.

Premature translation of the Drosophila zygotic genome activator Zelda is not sufficient to precociously activate gene expression.

Following fertilization, the unified germ cells rapidly transition to a totipotent embryo. Maternally deposited mRNAs encode the proteins necessary for this reprogramming as the zygotic genome remains transcriptionally quiescent during the initial stages of development. The transcription factors required to activate the zygotic genome are among these maternally deposited mRNAs and are robustly translated following fertilization. In Drosophila, the mRNA encoding Zelda, the major activator of the zygotic genome, is not translated until 1 h after fertilization. Here we demonstrate that zelda translation is repressed in the early embryo by the TRIM-NHL protein Brain tumor (BRAT). BRAT also regulates Zelda levels in the larval neuroblast lineage. In the embryo, BRAT-mediated translational repression is regulated by the Pan Gu kinase, which is triggered by egg activation. The Pan Gu kinase phosphorylates translational regulators, suggesting that Pan Gu kinase activity alleviates translational repression of zelda by BRAT and coupling translation of zelda with that of other regulators of early embryonic development. Using the premature translation of zelda in embryos lacking BRAT activity, we showed that early translation of a zygotic genome activator is not sufficient to drive precocious gene expression. Instead, Zelda-target genes showed increased expression at the time they are normally activated. We propose that transition through early development requires the integration of multiple processes, including the slowing of the nuclear division cycle and activation of the zygotic genome. These processes are coordinately controlled by Pan Gu kinase-mediated regulation of translation.

Measuring motivational interviewing self-efficacy of pre-service students completing a competency-based motivational interviewing course.

Background: Improving health outcomes requires health care practitioners to work collaboratively with clients to make healthy lifestyle changes. Motivational interviewing (MI) is an evidence-based approach found to evoke and support behavior change. Objective: The aim of this study was to examine changes over time in pre-service professional students' confidence in their MI skills after a 15-week interprofessional MI course. Methods: Students (N = 22) completed a newly developed 24-item Motivational Interviewing Confidence Survey (MICS pre and post participation in the course). Summary statistics, initial scale reliability assessment and t-tests were carried out. Results: MICS was a reliable measure (Cronbach's a = 0.98) and detected significant changes in students' self-perceived skill set. Using t-tests, significant differences were noted in pre- and post-assessments in students' confidence in their skills; students (p values<0.001) demonstrated significant gains in confidence on 23 of 24 MICS items. Conclusion: After participating in the course, students' confidence in their MI skills improved significantly. Adding pre-service training in MI may increase future healthcare practitioners' confidence in their MI skills and improve their capacity to engage in individually tailored, client-driven practice.

GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo.

Following fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are essential for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal-to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were required for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is necessary to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer-like factors, and we propose that as development proceeds control is gradually transferred from Zelda to GAF.

Most cells in an organism share the exact same genetic information, yet they still adopt distinct identities. This diversity emerges because only a selection of genes is switched on at any given time in a cell. Proteins that latch onto DNA control this specificity by activating certain genes at the right time. However, to perform this role they first need to physically access DNA: this can be difficult as the genetic information is tightly compacted so it can fit in a cell. A group of proteins can help to unpack the genome to uncover the genes that can then be accessed and activated. While these 'pioneer factors' can therefore shape the identity of a cell, much remains unknown about how they can work together to do so. For instance, the pioneer factor Zelda is essential in early fruit fly development, as it enables the genetic information of the egg and sperm to undergo dramatic reprogramming and generate a new organism. Yet, it was unclear whether additional helpers were required for this transition. Using this animal system, Gaskill, Gibson et al. identified GAGA Factor as a protein which works with Zelda to open up and reprogram hundreds of different sections along the genome of fruit fly embryos. This tag-team effort started with Zelda being important initially to activate genes; regulation was then handed over for GAGA Factor to continue the process. Without either protein, the embryo died. Getting a glimpse into early genetic events during fly development provides insights that are often applicable to other animals such as fish and mammals. Ultimately, this research may help scientists to understand how things can go wrong in human embryos.