NUDT7 regulates total hepatic CoA levels and the composition of the intestinal bile acid pool in male mice fed a Western diet.

Nudix hydrolase 7 (NUDT7) is an enzyme that hydrolyzes CoA species, is highly expressed in the liver, and resides in the peroxisomes. Peroxisomes are organelles where the preferential oxidation of dicarboxylic fatty acids occurs and where the hepatic synthesis of the primary bile acids cholic acid and chenodeoxycholic acid is completed. We previously showed that liver-specific overexpression of NUDT7 affects peroxisomal lipid metabolism but does not prevent the increase in total liver CoA levels that occurs during fasting. We generated Nudt7-/- mice to further characterize the role that peroxisomal (acyl-)CoA degradation plays in the modulation of the size and composition of the acyl-CoA pool and in the regulation of hepatic lipid metabolism. Here, we show that deletion of Nudt7 alters the composition of the hepatic acyl-CoA pool in mice fed a low-fat diet, but only in males fed a Western diet does the lack of NUDT7 activity increase total liver CoA levels. This effect is driven by the male-specific accumulation of medium-chain dicarboxylic acyl-CoAs, which are produced from the ß-oxidation of dicarboxylic fatty acids. We also show that, under conditions of elevated synthesis of chenodeoxycholic acid derivatives, Nudt7 deletion promotes the production of tauromuricholic acid, decreasing the hydrophobicity index of the intestinal bile acid pool and increasing fecal cholesterol excretion in male mice. These findings reveal that NUDT7-mediated hydrolysis of acyl-CoA pathway intermediates in liver peroxisomes contributes to the regulation of dicarboxylic fatty acid metabolism and the composition of the bile acid pool.

A Comparison of Self-reported Condomless Sex and Yc-DNA Biomarker Data from Young Women Engaged in High Risk Sexual Activity in Kampala, Uganda.

Reporting of condom-use can limit researchers' understanding of high-risk sexual behaviours. We compared self-reported condom-use with the Yc-DNA biomarker data and investigated potential factors influencing participation in, and reporting of, sexual behaviours. Self-reported data were collected using Audio Computer Assisted Self Interviews (ACASI) and samples for Yc-DNA biomarker were collected using self-administered and health worker-collected vaginal swabs from 644 women (aged 15-24 years) who were not living with HIV. Yc-DNA results and interview data were compared using McNemar-Bowker Analysis and Cohen's Kappa. Test statistics for Yc-DNA biomarker were calculated. Log Binomial models for Yc-DNA and self-reported results were conducted to assess for association. We found strong evidence (p < 0.001) for a difference between Yc-DNA and self-reported results. 13.7% of participants reported consistent condom-use with all partners, regardless of HIV status. Self-reported condom-use was discordant in 50.0% (n = 206) of cases, when compared to Yc-DNA results. Positive Yc-DNA results were found to be associated with older age (RR 1.36; 95%CI 1.04, 1.76 p = 0.023). Self-reported condom-use with partners with unknown HIV status was associated with higher education (RR 0.76; 95%CI 0.58,0.99 p = 0.043). Sensitivity analysis did not determine difference between methods for controlling for missing data. We found significant under-reporting of condomless sex in the self-reported data when compared to Yc-DNA results.

Aphantasia and autism: An investigation of mental imagery vividness.

OBJECTIVE: The present study investigated whether autistic adults report different levels of mental imagery vividness than non-autistic adults, and, moreover, if autism is associated with aphantasia which is defined as a condition of reduced or absent voluntary imagery. DESIGN AND METHODS: Clinically diagnosed and self-identifying autistic participants were compared with non-autistic participants in their mental imagery vividness (vision, sound, smell, taste, touch, bodily sensation and emotional feeling) and autistic traits using an online survey (N = 121). RESULTS: The autistic group scored significantly lower than the non-autistic group on imagery vividness (d = -0.44), in addition to having a higher proportion of participants scoring at cut-off for aphantasia. Moreover, a similar difference was observed for the emotional feel (η2 = 0.11). CONCLUSION: The vividness of visual and emotional mental imagery was on average lower for autistic individuals, with a higher proportion presenting at cut-off to be considered an aphantasic.

Integrating 'undetectable equals untransmittable' into HIV counselling in South Africa: the development of locally acceptable communication tools using intervention mapping.

BACKGROUND: The global campaign for "Undetectable equals Untransmittable" (U = U) seeks to spread awareness of HIV treatment as prevention, aiming to enhance psychological well-being and diminish stigma. Despite its potential benefits, U = U faces challenges in Sub-Saharan Africa, with low awareness and hesitancy to endorse it. We sought to develop a U = U communications intervention to support HIV counselling in primary healthcare settings in South Africa. METHODS: We used Intervention Mapping (IM), a theory-based framework to develop the "Undetectable and You" intervention for the South African context. The six steps of the IM protocol were systematically applied to develop the intervention including a needs assessment consisting of a systematic review and qualitative research including focus group discussions (FGD) and key informant (KI) interviews. Program objectives and target population were determined before designing the intervention components and implementation plan. RESULTS: The needs assessment indicated low global U = U awareness, especially in Africa, and scepticism about its effectiveness. Lay counsellors and clinic managers stressed the need for a simple and standardized presentation of U = U addressing both patients' needs for encouragement and modelling of U = U success but also clear guidance toward ART adherence behaviour. Findings from each step of the process informed successive steps. Our final intervention consisted of personal testimonials of PLHIV role models and their partners, organized as an App to deliver U = U information to patients in primary healthcare settings. CONCLUSIONS: We outline an intervention development strategy, currently in evaluation stage, utilizing IM with formative research and input from key U = U stakeholders and people living with HIV (PLHIV).

Trainee nursing associates in England: A multisite qualitative study of higher education institution perspectives.

AIM: To explore the experiences of university employees on the development and implementation of the nursing associate programme. BACKGROUND: As part of wider policy initiatives to address workforce shortages, provide progression for healthcare assistants and offer alternative routes into nursing, England recently introduced the nursing associate level of practice. Little research has yet considered university perspectives on this new programme. METHODS: An exploratory qualitative study reported following COREQ criteria. Twenty-seven university staff working with trainee nursing associates in five universities across England were recruited. Data, collected via semi-structured interviews from June to September 2021, were analysed through a combined framework and thematic analysis. RESULTS: Three themes developed: 'Centrality of partnerships' considered partnerships between employers and universities and changing power dynamics. 'Adapting for support' included responding to new requirements and changing pedagogical approaches. 'Negotiating identity' highlighted the university's role in advocacy and helping trainees develop a student identity. CONCLUSIONS: Nursing associate training in England has changed the dynamics between universities and healthcare employers, shifting learners' identity more to 'employee' rather than 'student'. Universities have adapted to support trainees in meeting academic and professional standards whilst also meeting employer expectations. While challenges remain, the ability of nurse educators to make adjustments, alongside their commitment to quality educational delivery, is helping establish this new training programme and thereby meet government policy initiatives. IMPLICATIONS FOR NURSING POLICY: The international movement of apprenticeship models in universities has the potential to change the status of the learner in nursing educational contexts. National policies that encourage this model should ensure that the implications and challenges this change of status brings to learners, employers and education institutions are fully considered prior to their implementation.

Risk factors for unsuppressed viral load after intensive adherence counseling among HIV infected persons in Kampala, Uganda: a nested case-control study.

BACKGROUND: Intensive adherence counseling (IAC) is the global standard of care for people living with human immunodeficiency virus (PLHIV) who have unsuppressed VL after ≥ 6 months of first-line anti-retroviral therapy (ART). We investigated whether the number of IAC sessions is associated with suppressed VL among PLHIV in Kampala, Uganda. METHODS: We conducted a nested case-control study among PLHIV with unsuppressed VL after ≥ 3 IAC sessions (cases) and a 2:1 random sample of PLHIV with suppressed VL after ≥ 3 IAC sessions (controls). Unsuppressed VL was defined as VL ≥ 1000 copies/ml. We performed multivariable logistic regression to identify factors that differed significantly between cases and controls. RESULTS: Demographic and clinical characteristics were similar among the 16 cases and 32 controls including mean age, sex, baseline CD4 count, VL before IAC, and WHO clinical stage. Only the number of IAC sessions differed significantly between cases and controls in unadjusted (p = 0.012) and adjusted (p = 0.016) analyses. Each unit increase in IAC session was associated with unsuppressed VL (Adjusted odds ratio 5.09; 95% CI 1.35-19.10). CONCLUSIONS: VL remained unsuppressed despite increasing IAC frequency. The fidelity to standardized IAC protocol besides drug resistance testing among PLHIV with unsuppressed VL before IAC commencement should be examined.

Should I stay or should I go? Why nurses are leaving community nursing in the UK.

Worsening working conditions for nursing workforce has seen a massive exodus of staff, particularly in community nursing in the UK. AIM: The study aim was to map working conditions as well as identify differentiating characteristics of community nurses that intend to leave their profession. DESIGN: Eligibility criteria were community nurses working in all 4 UK countries. All data was collected by means of a cross-sectional survey via the largest closed, private community nursing online-forum. Logistic regression was carried out to ascertain the effects of the variables on the intention to leave. RESULTS: The total number of respondents was 533. Findings showed that one in two of all community nurses (≈46%) are reporting job dissatisfaction. Length of unpaid overtime per shift (odds increase by 30% for each hour of overtime), manager support, proportion of permanent staff, team size, shift length, travel mileage, worsened conditions in the last year and overall self-rated working conditions were differentiating factors between those that intended to leave the job. The proportion of permanent staff on the team and perceived lack of support from management best predicted the likelihood of leave rates. Our findings imply that low nurse retention will fuel an even higher exodus because job dissatisfaction is highest on teams with lowest permanent staff ratios. Poor management that is inept at supporting frontline staff means that the fundamental retention issues are exacerbated and will not stop the unprecedented crisis that is predicted to lead to a collapse of care provision in community settings. Nurses play a central role and are 'key' to delivering the much- desired patient-centred care' therefore their well-being and job satisfaction should become a priority for policymakers.

Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions.

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies.

Screening for Hepatitis B in partners and children of women positive for surface antigen, Burkina Faso.

Objective: To evaluate the implementation of a screening strategy for the partners and children of pregnant women with hepatitis B virus (HBV) attending antenatal care. Methods: We identified pregnant women positive for HBV surface antigen (HBsAg) at antenatal consultation in Ouagadougou, Burkina Faso. At post-test counselling, women were advised to disclose their HBV status to partners and to encourage their partner and children to be screened for HBsAg. We used multivariable logistic regression to explore factors associated with uptake of screening and HBsAg positivity among family members. Findings: Of 1000 HBsAg-positive women, 436/1000 partners and 215/1281 children were screened. HBsAg was detected in 55 (12.6%) partners and 24 (11.2%) children. After adjusting for confounders, uptake of screening was higher in partners who were married, who attended the woman's first post-test consultation and to whom the woman had disclosed her HBV status. In children, HBsAg positivity was associated with being born before the introduction of infant hepatitis B vaccination in Burkina Faso (not significant in the multivariable analysis), having a mother positive for HBV e-antigen (adjusted OR: 8.57; 95% CI: 2.49-29.48) or having a mother with HBV DNA level ≥ 200 000 IU/mL (OR: 6.83; 95% CI: 1.61-29.00). Conclusion: In low-income countries, the antenatal consultation provides a cost-effective opportunity to identify HBV-infected household contacts and link them to care. Children born before the introduction of infant hepatitis B vaccination and whose mother has higher viral load or infectivity should be a priority for testing and linkage to care.

Willingness to pay for an mHealth anti-retroviral therapy adherence and information tool: Transitioning to sustainability, Call for life randomised study experience in Uganda.

INTRODUCTION: Evidence shows benefit of digital technology for people living with human immunodeficiency virus on antiretroviral therapy adherence and retention in care, however, scalability and sustainability have scarcely been evaluated. We assessed participants' willingness to pay a fee for mHealth "Call for life Uganda" support, a mobile-phone based tool with the objective to assess sustainability and scalability. METHODS: "Call for Life study", approved by Makerere University, School of Public Health research & ethics committee, at 2 sites in Uganda, evaluated a MoTech based software "CONNECT FOR LIFE™" mHealth tool termed "Call for life Uganda". It provides short messages service or Interactive Voice Response functionalities, with a web-based interface, allows a computer to interact with humans through use of voice and tones input via keypad. Participants were randomized at 1:1 ratio to Standard of Care or standard of care plus Call for life Uganda. This sends pill reminders, visit reminders, voice messages and self-reported symptom support. At study visits 18 and 24 months, through mixed method approach we assessed mHealth sustainability and scalability. Participants were interviewed on desire to have or continue adherence support and willingness to pay a nominal fee for tool. We computed proportions willing to pay (± 95% confidence interval), stratified by study arm and predictors of willingness to continue and to pay using multivariate logistic regression model backed up by themes from qualitative interviews. RESULTS: 95% of participants were willing to continue using C4LU with 77.8% willing to pay for the service. Persons receiving care at the peri-urban clinic (OR 3.12, 95% CI 1.43-9.11.86) and those with exposure to the C4LU intervention (OR 4.2, 95% CI 1.55-11.84) were more likely to continue and pay for the service. Qualitative interviews revealed mixed feelings regarding amounts to pay, those willing to pay, argued that since they have been paying for personal phone calls/messages, they should not fail to pay for Call for life. CONCLUSIONS: Payment for the service offers opportunities to scale up and sustain mHealth interventions which may not be priorities for government funding. A co-pay model could be acceptable to PLHIV to access mHealth services in low resource settings. Clinical Trial Number NCT02953080.

Fusion of Heterogenous Sensor Data in Border Surveillance.

Wide area surveillance has become of critical importance, particularly for border control between countries where vast forested land border areas are to be monitored. In this paper, we address the problem of the automatic detection of activity in forbidden areas, namely forested land border areas. In order to avoid false detections, often triggered in dense vegetation with single sensors such as radar, we present a multi sensor fusion and tracking system using passive infrared detectors in combination with automatic person detection from thermal and visual video camera images. The approach combines weighted maps with a rule engine that associates data from multiple weighted maps. The proposed approach is tested on real data collected by the EU FOLDOUT project in a location representative of a range of forested EU borders. The results show that the proposed approach can eliminate single sensor false detections and enhance accuracy by up to 50%.

Understanding the value of a PhD for post-doctoral registered UK nurses: A survey.

AIMS: This study investigated, 'What is the perceived value of a PhD to doctoral and postdoctoral nurses in the UK?' BACKGROUND: Little is known about what happens to the careers of nurses who undertake a doctorate and whether they use these skills in the next career steps. METHODS: Nurses (n = 47) with doctorates were recruited via professional networks and twitter (@NMAHP_DoctorateStudy). Qualitative responses from the nurses were analysed using thematic analysis. RESULTS: Three themes emerged from qualitative analysis: impact on career, utilization and value, and impact on self. CONCLUSIONS: This study provides one of the few insights into how doctoral trained nurses understand and experience the value and utility of their studies to themselves and others. IMPLICATIONS FOR NURSE MANAGEMENT: Nurse managers can play a crucial role in generating a research-led culture within their clinical setting. This would include promoting an understanding of research as something directly related to patient benefit rather than an abstract, intellectual activity.

Delays in reporting and publishing trial results during pandemics: cross sectional analysis of 2009 H1N1, 2014 Ebola, and 2016 Zika clinical trials.

BACKGROUND: Pandemic events often trigger a surge of clinical trial activity aimed at rapidly evaluating therapeutic or preventative interventions. Ensuring rapid public access to the complete and unbiased trial record is particularly critical for pandemic research given the urgent associated public health needs. The World Health Organization (WHO) established standards requiring posting of results to a registry within 12 months of trial completion and publication in a peer reviewed journal within 24 months of completion, though compliance with these requirements among pandemic trials is unknown. METHODS: This cross-sectional analysis characterizes availability of results in trial registries and publications among registered trials performed during the 2009 H1N1 influenza, 2014 Ebola, and 2016 Zika pandemics. We searched trial registries to identify clinical trials testing interventions related to these pandemics, and determined the time elapsed between trial completion and availability of results in the registry. We also performed a comprehensive search of MEDLINE via PubMed, Google Scholar, and EMBASE to identify corresponding peer reviewed publications. The primary outcome was the compliance with either of the WHO's established standards for sharing clinical trial results. Secondary outcomes included compliance with both standards, and assessing the time elapsed between trial completion and public availability of results. RESULTS: Three hundred thirty-three trials met eligibility criteria, including 261 H1N1 influenza trials, 60 Ebola trials, and 12 Zika trials. Of these, 139 (42%) either had results available in the trial registry within 12 months of study completion or had results available in a peer-reviewed publication within 24 months. Five trials (2%) met both standards. No results were available in either a registry or publication for 59 trials (18%). Among trials with registered results, a median of 42 months (IQR 16-76 months) elapsed between trial completion and results posting. For published trials, the median elapsed time between completion and publication was 21 months (IQR 9-34 months). Results were available within 24 months of study completion in either the trial registry or a peer reviewed publication for 166 trials (50%). CONCLUSIONS: Very few trials performed during prior pandemic events met established standards for the timely public dissemination of trial results.

Changing Knowledge and Attitudes Towards HIV Treatment-as-Prevention and "Undetectable = Untransmittable": A Systematic Review.

People on HIV treatment with undetectable virus cannot transmit HIV sexually (Undetectable = Untransmittable, U = U). However, the science of treatment-as-prevention (TasP) may not be widely understood by people with and without HIV who could benefit from this information. We systematically reviewed the global literature on knowledge and attitudes related to TasP and interventions providing TasP or U = U information. We included studies of providers, patients, and communities from all regions of the world, published 2008-2020. We screened 885 papers and abstracts and identified 72 for inclusion. Studies in high-income settings reported high awareness of TasP but gaps in knowledge about the likelihood of transmission with undetectable HIV. Greater knowledge was associated with more positive attitudes towards TasP. Extant literature shows low awareness of TasP in Africa where 2 in 3 people with HIV live. The emerging evidence on interventions delivering information on TasP suggests beneficial impacts on knowledge, stigma, HIV testing, and viral suppression.Review was pre-registered at PROSPERO: CRD42020153725.

RESUMEN: Las personas en tratamiento contra el VIH con virus indetectable no pueden transmitir el VIH sexualmente (indetectable = intransmisible, U = U por sus siglas en inglés). Pero, la ciencia del tratamiento como prevención (TasP, por sus siglas en inglés) puede que no sea ampliamente comprendida por personas con y sin VIH que podrían beneficiarse. Revisamos sistemáticamente la literatura mundial sobre conocimientos y actitudes relacionados con TasP e intervenciones que proporcionan información TasP o U = U, 2008­2020. Incluimos estudios de proveedores, pacientes y comunidades de todas las regiones del mundo. Se examinaron 885 artículos y resúmenes y se identificaron 72 para su inclusión. Los estudios en entornos de ingresos altos informaron un alto conocimiento de TasP pero existen lagunas en el conocimiento sobre la probabilidad de transmisión del VIH indetectable. Un mayor conocimiento se asoció con actitudes más positivas hacia TasP. La literatura existente muestra un escaso conocimiento de TasP en África, donde viven 2 de cada 3 personas con VIH. La evidencia emergente sobre intervenciones que brindan información sobre TasP sugiere impactos positivos en el conocimiento, el estigma, las pruebas del VIH y la supresión viral.

Prevalence of undetectable and suppressed viral load in HIV-infected pregnant women initiating Option B+ in Uganda: an observational study nested within a randomized controlled trial.

BACKGROUND: Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). METHODS: Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. RESULTS: The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants' age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416-0.982). CONCLUSION: Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be "elite controllers" or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

Shortcuts in knowledge mobilization: An ethnographic study of advanced nurse practitioner discharge decision-making in the emergency department.

AIM: To understand how advanced nurse practitioners use knowledge to inform their discharge decision-making in the emergency department. BACKGROUND: Advanced nurse practitioner roles have developed globally in a wide range of healthcare settings, including the emergency department, over the past few years. The scope of practice and training vary widely between countries. Little is known about how they use clinical knowledge in the emergency department. DESIGN: An ethnographic study was undertaken in an emergency department in the North of England. METHOD: Data were collected by observation (n = 5) and semi-structured interviews (n = 13) between September 2016 and June 2017. Interview transcripts and field notes were coded using Quirkos software. Thematic analysis was used to identify key themes. FINDINGS: In boundary blurring with medicine, advanced nurse practitioners in the emergency department need to make timely, autonomous discharge decisions. Knowledge mobilization is messy and complex; however, shortcuts facilitate autonomous discharge decision-making. More experienced advanced nurse practitioners rely less on shortcuts as they draw on experiential knowledge. DISCUSSION: Boundary blurring in the advanced nurse practitioner role in the emergency department, requires reliable knowledge shortcuts. Support from senior colleagues and accessible smartphone apps enable advanced nurse practitioners to efficiently make discharge decisions. This study adds to previous research on how knowledge is managed in boundary blurring. CONCLUSION: Advanced nurse practitioners in the emergency department require timely access to relevant, up to date knowledge. This study has highlighted their preferred knowledge sources to inform discharge decision-making. In boundary blurring, shortcuts enable ANPs to use knowledge efficiently to inform patient care in the emergency department. IMPACT: The findings increase our understanding of how to equip advanced nurse practitioners with knowledge to facilitate clinical decision-making. Clinical managers should provide mentorship and relevant up to date knowledge shortcuts to ensure efficient, evidence-based discharge decision-making.

Secondary Palate Development in the Dog (Canis lupus familiaris).

OBJECTIVE: To investigate the gestational timing of morphologic events in normal canine secondary palate development as a baseline for studies in dog models of isolated cleft palate (CP). METHODS: Beagle and beagle/cocker spaniel-hybrid fetal dogs were obtained by cesarean-section on various days of gestation, timed from the initial rise of serum progesterone concentration. Morphology of fetal heads was determined by examining serial coronal sections. RESULTS: On gestational day 35 (d35), the palatal shelves pointed ventrally alongside the tongue. On d36, palatal shelves were elongated and elevated to a horizontal position above the tongue but were not touching. On d37, palatine shelves and vomer were touching, but the medial epithelial seam (MES) between the apposed shelves remained. Immunostaining with epithelial protein markers showed that the MES gradually dissolved and was replaced by mesenchyme during d37-d44, and palate fusion was complete by d44. Examination of remnant MES suggested that fusion of palatal shelves began in mid-palate and moved rostrally and caudally. CONCLUSION: Palate development occurs in dogs in the steps described in humans and mice, but palate closure occurs at an intermediate time in gestation. These normative data will form the basis of future studies to determine pathophysiologic mechanisms in dog models of CP. Added clinical significance is the enhancement of dogs as a large animal model to test new approaches for palate repair, with the obvious advantage of achieving full maturity within 2 years rather than 2 decades.

Sources of satisfaction, dissatisfaction and well-being for UK advanced practice nurses: A qualitative study.

AIMS: To examine and explore organisational and role conditions that promote or inhibit job satisfaction and workplace well-being for advanced practice nurses. BACKGROUND: The advanced practice role is common across the world. Research shows it is well regarded by patients and improves patient outcomes, but there is little evidence about what the role is like for nurses. METHODS: A subsample of an existing cohort of advanced practice nurses were invited for interview. Twenty-two nurses were interviewed over the phone. Interviews transcripts were analysed using thematic analysis. RESULTS: Four themes were derived from the data; 'the advanced nurse role and professional identity', 'feeling exposed', 'support for the advancement of the role' and 'demonstrating impact'. CONCLUSION: Nurses report considerable dissatisfaction with role identity and concerns relating to isolation on a daily basis, and these negatively affect well-being. However, they also identified significant satisfaction with the role, particularly when well supported and able to recognize the unique contribution that they made to the lives of patients and to their organisations. IMPLICATIONS FOR NURSING MANAGEMENT: Clear role definitions, provision of high-quality clinical supervision and addressing issues of isolation are likely to improve the job satisfaction of advanced practice nurses.

Obese Youth Demonstrate Altered Landing Knee Mechanics Unrelated to Lower-Extremity Peak Torque When Compared With Healthy Weight Youth.

Obese (OB) youth demonstrate altered knee mechanics and worse lower-extremity performance compared with healthy weight (HW) youth. Our objectives were to compare sagittal plane knee landing mechanics between OB and HW youth and to examine the associations of knee and hip extension peak torque with landing mechanics in OB youth. Twenty-four OB and 24 age- and sex-matched HW youth participated. Peak torque was measured and normalized to leg lean mass. Peak knee flexion angle and peak internal knee extension moment were measured during a single-leg hop landing. Paired t tests, Pearson correlation coefficients, and Bonferroni corrections were used. OB youth demonstrated worse performance and lower knee extension (OB: 12.76 [1.38], HW: 14.03 [2.08], P = .03) and hip extension (OB: 8.59 [3.13], HW: 11.10 [2.89], P = .005) peak torque. Furthermore, OB youth demonstrated lower peak knee flexion angles (OB: 48.89 [45.41 to 52.37], HW: 56.07 [52.59 to 59.55], P = .02) and knee extension moments (OB: -1.73 [-1.89 to -1.57], HW: -2.21 [-2.37 to -2.05], P = .0001) during landing compared with HW youth. Peak torque measures were not correlated with peak knee flexion angle nor internal knee extension moment during landing in either group (P > .01). OB youth demonstrated altered landing mechanics compared with HW youth. However, no associations among peak torque measurements and knee landing mechanics were present.

Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition.

BACKGROUND: High-quality epidemiologic data worldwide are needed to improve our understanding of disease risk, support health policy to meet the diverse needs of people with multiple sclerosis (MS) and support advocacy efforts. OBJECTIVES: The Atlas of MS is an open-source global compendium of data regarding the epidemiology of MS and the availability of resources for people with MS reported at country, regional and global levels. METHODS: Country representatives reported epidemiologic data and their sources via survey between September 2019 and March 2020, covering prevalence and incidence in males, females and children, and age and MS type at diagnosis. Regional analyses and comparisons with 2013 data were conducted. RESULTS: A total of 2.8 million people are estimated to live with MS worldwide (35.9 per 100,000 population). MS prevalence has increased in every world region since 2013 but gaps in prevalence estimates persist. The pooled incidence rate across 75 reporting countries is 2.1 per 100,000 persons/year, and the mean age of diagnosis is 32 years. Females are twice as likely to live with MS as males. CONCLUSIONS: The global prevalence of MS has risen since 2013, but good surveillance data is not universal. Action is needed by multiple stakeholders to close knowledge gaps.