An immunodominant NP105-113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease.

NP105-113-B*07:02-specific CD8+ T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP105-113-B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP105-113-B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP105-113-B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP105-113-B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.

Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus-like particles (VLPs) containing HIV-1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV-G). cGAMP loading of VLPs augments CD4 and CD8 T-cell responses. It also increases VLP- and VSV-G-specific antibody titres in a STING-dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS-CoV-2 Spike protein enhances Spike-specific antibody titres. cGAMP-loaded VLPs are thus an attractive platform for vaccination.

Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.

Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.

The risk of all-cause mortality associated with anxiety: a retrospective cohort study using 'The Health Improvement Network' database.

BACKGROUND: Anxiety is a prevalent condition with a substantial associated burden of morbidity. Previous literature investigating effects of anxiety on mortality rates has found conflicting results. This is in part due to inadequate consideration of comorbid depression as a confounder and analysing sub-types of anxiety together. The objective of this study was to compare mortality risks in people diagnosed with anxiety. METHODS: We undertook a retrospective cohort study using the 'The Health Improvement Network' database (a UK primary care dataset) between 1st January 2005 to 1st January 2018. 345 903 patients with anxiety (exposed group) were matched to 691 449 unexposed patients. Cox regression analyses were used to adjusted hazard ratios (HRs) for mortality risk. RESULTS: During the study period 18 962 patients (5·5%) died in the exposed group compared to 32 288 (4·7%) in the unexposed group. This translated into a crude HR for all of 1·14 (95% CI 1·12 - 1·16), which remained significant after adjustment for key co-variates (including depression) giving a final HR of 1·05 (95% CI 1·03 - 1·07). When broken down by sub-type of anxiety (10·3% (35, 581) had phobias, 82·7% (385,882) has 'other' types, and 7·0% (24,262) had stress related anxiety) there were markedly different effect sizes. The adjusted model for the stress-related anxiety sub-type demonstrated a HR of 0·88 (95% CI 0·80 - 0·97). Conversely, the HR was increased in 'other' sub-types to 1·07 (95% CI 1·05 - 1·09) and non-significant in phobia types of anxiety. CONCLUSION: A complex relationship is found between anxiety and mortality. The presence of anxiety slightly increased the risk of death, but this risk varies depending on the type of anxiety diagnosed.

Community-based approaches to infant safe sleep and breastfeeding promotion: a qualitative study.

BACKGROUND: In the U.S., sudden unexpected infant deaths (SUID) due to accidental suffocation and strangulation in bed (ASSB) are increasing, with disparities by race/ethnicity. While breastfeeding is a protective factor against infant mortality, racial/ethnic disparities are present in its uptake, and motivations to breastfeed are also often coupled with non-recommended infant sleep practices that are associated with infant sleep deaths. Combining infant safe sleep (ISS) and breastfeeding promotion on the community level presents opportunities to address racial/ethnic disparities and associated socioeconomic, cultural, and psychosocial influences. METHODS: We completed a descriptive qualitative hermeneutical phenomenology using thematic analysis of focus group data. We examined the phenomenon of community-level providers promoting ISS and breastfeeding in communities vulnerable to ISS and breastfeeding disparities. We asked eighteen informants participating in a national quality improvement collaborative about i.) areas requiring additional support to meet community needs around ISS and breastfeeding, and ii.) recommendations on tools to improve their work promoting ISS and breastfeeding. RESULTS: We identified four themes: i.) education and dissemination, ii.) relationship building and social support, iii.) working with clients' personal circumstances and considerations, and iv.) tools and systems. CONCLUSIONS: Our findings support embedding risk-mitigation approaches in ISS education; relationship building between providers, clients, and peers; and the provision of ISS and breastfeeding supportive material resources with educational opportunities. These findings may be used to inform community-level provider approaches to ISS and breastfeeding promotion.

Pregnant Latinas' perspectives on pursuing expanded carrier screening: "It is better to know than not".

With the advance of genetic technologies, the use of expanded carrier screening (ECS) in the prenatal setting is growing. ECS tests for a wide range of inherited genetic disorders regardless of racial/ethnic background and family history. Latinxs are an important ECS stakeholder group as they are the largest minority group with the highest fertility rate in the United States. Yet, the Latinx population has, to date, been underrepresented and understudied in genetics/genomics research. We conducted a study to explore the knowledge and perspectives of pregnant Latinas regarding ECS in which descriptive statistics and content analysis were used to analyze the data. Thirty-two pregnant Latinas - mostly of low educational levels (no education beyond high school) and with less than $20,000 annual household income living in rural areas were surveyed, provided with education about ECS, and interviewed. Participants were found to possess limited knowledge about ECS prior to being interviewed. Most (68.8%), however, expressed interest in pursuing ECS following the educational component that explained ECS. Their interest was mainly driven by the desire to know their baby's chance of developing a genetic disorder, the low risk of ECS procedures for both pregnant Latinas and their fetus, and the opportunity to better prepare for raising a child with a genetic condition. Our findings contribute to the limited research in the genetics/genomics field by providing in-depth insights into the perspectives of pregnant Latinas regarding ECS. Obstetric providers and genetic counselors should provide culturally appropriate education and counseling to empower pregnant Latinas to make informed decisions about the use of ECS.

mTOR Regulation of N-Myc Downstream Regulated 1 (NDRG1) Phosphorylation in Clear Cell Renal Cell Carcinoma.

The mechanistic target of rapamycin (mTOR) kinase is a component of two signaling complexes that are known as mTOR complex 1 (mTORC1) and mTORC2. We sought to identify mTOR-phosphorylated proteins that are differently expressed in clinically resected clear cell renal cell carcinoma (ccRCC) relative to pair-matched normal renal tissue. Using a proteomic array, we found N-Myc Downstream Regulated 1 (NDRG1) showed the greatest increase (3.3-fold) in phosphorylation (on Thr346) in ccRCC. This was associated with an increase in total NDRG1. RICTOR is a required subunit in mTORC2, and its knockdown decreased total and phospho-NDRG1 (Thr346) but not NDRG1 mRNA. The dual mTORC1/2 inhibitor, Torin 2, significantly reduced (by ~100%) phospho-NDRG1 (Thr346). Rapamycin is a selective mTORC1 inhibitor that had no effect on the levels of total NDRG1 or phospho-NDRG1 (Thr346). The reduction in phospho-NDRG1 (Thr346) due to the inhibition of mTORC2 corresponded with a decrease in the percentage of live cells, which was correlated with an increase in apoptosis. Rapamycin had no effect on ccRCC cell viability. Collectively, these data show that mTORC2 mediates the phosphorylation of NDRG1 (Thr346) in ccRCC. We hypothesize that RICTOR and mTORC2-mediated phosphorylation of NDRG1 (Thr346) promotes the viability of ccRCC cells.

Navigating dietary advice for multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory demyelinating disease with no known cure. Numerous diets are promoted to reduce symptoms or even cure MS, despite insufficient evidence for any therapeutic diet. There are few qualitative studies exploring the experiences of people with MS in relation to diet, and no use of theory to explain the findings. PURPOSE: To explore the experiences of adults with MS when navigating dietary advice, their attitudes when making dietary decisions, and their needs regarding dietary resources and education. METHODS: In this qualitative study, we conducted six focus groups with people with MS (n = 33 plus one spouse without MS). Groups were audio-recorded and transcribed verbatim. Primary analysis used a general inductive approach with thematic analysis. Secondary analysis aligned themes with the constructs of the self-determination theory. RESULTS: Six themes emerged: (a) confusion about where to seek dietary advice; (b) scepticism towards national dietary guidelines; (c) personalized approaches to dietary change; (d) barriers to dietary changes; (e) judging if dietary changes work; and (f) wanting dietary guidelines for MS. CONCLUSION: People with MS are highly motivated to make dietary changes and improve their health. The self-determination theory explained why people with MS make dietary modifications, and the varying levels of motivation. MS-specific dietary resources and nutrition education need to incorporate ways to increase autonomous forms of motivation. Future dietary intervention studies could use the self-determination theory as a framework to improve long-term adherence to healthier diets.

The Adipose Tissue-Derived Secretome (ADS) in Obesity Uniquely Induces L-Type Amino Acid Transporter 1 (LAT1) and mTOR Signaling in Estrogen-Receptor-Positive Breast Cancer Cells.

Obesity increases the risk of postmenopausal breast cancer (BC). This risk is mediated by obesity-induced changes in the adipose-derived secretome (ADS). The pathogenesis of BC in obesity is stimulated by mTOR hyperactivity. In obesity, leucine might support mTOR hyperactivity. Leucine uptake by BC cells is through L-Type Amino Acid Transporter 1 (LAT1). Our objective was to link obesity-ADS induction of LAT1 to the induction of mTOR signaling. Lean- and obese-ADS were obtained from lean and obese mice, respectively. Breast ADS was obtained from BC patients. Estrogen-receptor-positive BC cells were stimulated with ADS. LAT1 activity was determined by uptake of 3H-leucine. The LAT1/CD98 complex, and mTOR signaling were assayed by Western blot. The LAT1 antagonists, BCH and JPH203, were used to inhibit LAT1. Cell migration and invasion were measured by Transwell assays. The results showed obese-ADS-induced LAT1 activity by increasing transporter affinity for leucine. Consistent with this mechanism, LAT1 and CD98 expression were unchanged. Induction of mTOR by obese-ADS was inhibited by LAT1 antagonists. Breast ADS from patients with BMIs > 30 stimulated BC cell migration and invasiveness. Collectively, our findings show that obese-ADS induction of LAT1 supports mTOR hyperactivity in luminal BC cells.

Structural and immunologic correlates of chemically stabilized HIV-1 envelope glycoproteins.

Inducing broad spectrum neutralizing antibodies against challenging pathogens such as HIV-1 is a major vaccine design goal, but may be hindered by conformational instability within viral envelope glycoproteins (Env). Chemical cross-linking is widely used for vaccine antigen stabilization, but how this process affects structure, antigenicity and immunogenicity is poorly understood and its use remains entirely empirical. We have solved the first cryo-EM structure of a cross-linked vaccine antigen. The 4.2 Å structure of HIV-1 BG505 SOSIP soluble recombinant Env in complex with a CD4 binding site-specific broadly neutralizing antibody (bNAb) Fab fragment reveals how cross-linking affects key properties of the trimer. We observed density corresponding to highly specific glutaraldehyde (GLA) cross-links between gp120 monomers at the trimer apex and between gp120 and gp41 at the trimer interface that had strikingly little impact on overall trimer conformation, but critically enhanced trimer stability and improved Env antigenicity. Cross-links were also observed within gp120 at sites associated with the N241/N289 glycan hole that locally modified trimer antigenicity. In immunogenicity studies, the neutralizing antibody response to cross-linked trimers showed modest but significantly greater breadth against a global panel of difficult-to-neutralize Tier-2 heterologous viruses. Moreover, the specificity of autologous Tier-2 neutralization was modified away from the N241/N289 glycan hole, implying a novel specificity. Finally, we have investigated for the first time T helper cell responses to next-generation soluble trimers, and report on vaccine-relevant immunodominant responses to epitopes within BG505 that are modified by cross-linking. Elucidation of the structural correlates of a cross-linked viral glycoprotein will allow more rational use of this methodology for vaccine design, and reveals a strategy with promise for eliciting neutralizing antibodies needed for an effective HIV-1 vaccine.

Female survivors of intimate partner violence and risk of depression, anxiety and serious mental illness.

BACKGROUND: Internationally, intimate partner violence (IPV) cohorts have demonstrated associations with depression and anxiety. However, this association has not yet been described in a UK population, nor has the association with serious mental illness (SMI). AIMS: To explore the relationship between IPV exposure and mental illness in a UK population. METHOD: We designed a retrospective cohort study whereby we matched 18 547 women exposed to IPV to 74 188 unexposed women. Outcomes of interest (anxiety, depression and SMI) were identified through clinical codes. RESULTS: At baseline, 9174 (49.5%) women in the exposed group had some form of mental illness compared with 17 768 (24.0%) in the unexposed group, described as an adjusted odds ratio of 2.62 (95% CI 2.52-2.72). Excluding those with mental illness at baseline, 1254 exposed women (incidence rate 46.62 per 1000 person-years) went on to present with any type of mental illness compared with 3119 unexposed women (incidence rate 14.93 per 1000 person-years), with an aIRR of 2.77 (95% CI 2.58-2.97). Anxiety (aIRR 1.99, 95% CI 1.80-2.20), depression (aIRR 3.05, 95% CI 2.81-3.31) and SMI (aIRR 3.08, 95% CI 2.19-4.32) were all associated with exposure to IPV. CONCLUSIONS: IPV remains a significant public health issue in the UK. We have demonstrated the significant recorded mental health burden associated with IPV in primary care, at both baseline and following exposure. Clinicians must be aware of this association to reduce mental illness diagnostic delay and improve management of psychological outcomes in this group of patients.

Improving the Efficiency and Effectiveness of Parent Education in the Neonatal Intensive Care Unit.

BACKGROUND: March of Dimes partners with hospitals across the country to implement NICU Family Support (NFS) Core Curriculum, a program providing education to parents in neonatal intensive care units (NICUs) across the country. PURPOSE: This NFS project's goal was to increase the efficiency and effectiveness of NICU parent education by establishing consistency, improving quality, and identifying best practices. METHODS/SEARCH STRATEGY: A 5 topic curriculum was developed and implemented across NFS program sites. The project studied 4 main outcomes of interest related to efficiency and effectiveness: increase in parenting confidence, parent learning, knowledge change, and satisfaction. Data were collected from speakers and attendees immediately following educational sessions. Analytical approaches included descriptive statistics such as frequency, percentage, and response rate, and inferential approaches such as t test, χ, and analysis of variance. FINDINGS/RESULTS: Findings suggest that the NFS Core Curriculum improved both program efficiency and effectiveness. Sessions fully implemented according to recommended strategies had better outcomes than sessions not fully implemented according to recommended strategies (P < .0001). Across the 3648 attendees at 41 sites, 77% of parents reported learning "a lot" at the session they attended and 85% of attendees reported increased confidence. Attendees also reported positive knowledge change and high satisfaction. IMPLICATIONS FOR PRACTICE: Parent education best practices identified through this initiative can be utilized for future NFS Core Curriculum topics and potentially generalized to all NICU parent education and family education in other hospital intensive care units. IMPLICATIONS FOR RESEARCH: Content and best practices identified through this project will require regular review to ensure medical accuracy and appropriateness of best practices as the physical design of NICUs evolves.

Chemical Cross-Linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein Trimer Antigens.

UNLABELLED: Major neutralizing antibody immune evasion strategies of the HIV-1 envelope glycoprotein (Env) trimer include conformational and structural instability. Stabilized soluble trimers such as BG505 SOSIP.664 mimic the structure of virion-associated Env but nevertheless sample different conformational states. Here we demonstrate that treating BG505 SOSIP.664 trimers with glutaraldehyde or a heterobifunctional cross-linker introduces additional stability with relatively modest effects on antigenicity. Thus, most broadly neutralizing antibody (bNAb) epitopes were preserved after cross-linking, whereas the binding of most weakly or nonneutralizing antibodies (non-NAb) was reduced. Cross-linking stabilized all Env conformers present within a mixed population, and individual conformers could be isolated by bNAb affinity chromatography. Both positive selection of cross-linked conformers using the quaternary epitope-specific bNAbs PGT145, PGT151, and 3BC315 and negative selection with non-NAbs against the V3 region enriched for trimer populations with improved antigenicity for bNAbs. Similar results were obtained using the clade B B41 SOSIP.664 trimer. The cross-linking method may, therefore, be useful for countering the natural conformational heterogeneity of some HIV-1 Env proteins and, by extrapolation, also vaccine immunogens from other pathogens. IMPORTANCE: The development of a vaccine to induce protective antibodies against HIV-1 is of primary public health importance. Recent advances in immunogen design have provided soluble recombinant envelope glycoprotein trimers with near-native morphology and antigenicity. However, these trimers are conformationally flexible, potentially reducing B-cell recognition of neutralizing antibody epitopes. Here we show that chemical cross-linking increases trimer stability, reducing binding of nonneutralizing antibodies while largely maintaining neutralizing antibody binding. Cross-linking followed by positive or negative antibody affinity selection of individual stable conformational variants further improved the antigenic and morphological characteristics of the trimers. This approach may be generally applicable to HIV-1 Env and also to other conformationally flexible pathogen antigens.

Association Between Infant Mortality Attributable to Birth Defects and Payment Source for Delivery - United States, 2011-2013.

Birth defects are a leading cause of infant mortality in the United States (1), accounting for approximately 20% of infant deaths. The rate of infant mortality attributable to birth defects (IMBD) in the United States in 2014 was 11.9 per 10,000 live births (1). Rates of IMBD differ by race/ethnicity (2), age group at death (2), and gestational age at birth (3). Insurance type is associated with survival among infants with congenital heart defects (CHD) (4). In 2003, a checkbox indicating principal payment source for delivery was added to the U.S. standard birth certificate (5). To assess IMBD by payment source for delivery, CDC analyzed linked U.S. birth/infant death data for 2011-2013 from states that adopted the 2003 revision of the birth certificate. The results indicated that IMBD rates for preterm (<37 weeks of gestation) and term (≥37 weeks) infants whose deliveries were covered by Medicaid were higher during the neonatal (<28 days) and postneonatal (≥28 days to <1 year) periods compared with infants whose deliveries were covered by private insurance. Similar differences in postneonatal mortality were observed for the three most common categories of birth defects listed as a cause of death: central nervous system (CNS) defects, CHD, and chromosomal abnormalities. Strategies to ensure quality of care and access to care might reduce the difference between deliveries covered by Medicaid and those covered by private insurance.

A new genus of rhinebothriidean cestodes from batoid elasmobranchs, with the description of five new species and two new combinations.

Survey work of batoid elasmobranchs in the eastern Atlantic and Indo-Pacific revealed multiple species of a new genus of cestode. Stillabothrium Healy et Reyda gen. n. (Rhinebothriidea: Escherbothriidae) is unique in its possession of an even number of non-medial longitudinal septa in the posterior portion of the bothridia, resulting in a series of loculi that are longer than wide (i.e. vertically oriented) and are arranged in columns. Five new species of Stillabothrium are described, S. ashleyae Willsey et Reyda sp. n., S. davidcynthiaorum Daigler et Reyda sp. n., S. campbelli Delgado, Dedrick et Reyda sp. n., S. hyphantoseptum Herzog, Bergman et Reyda sp. n., S. jeanfortiae Forti, Aprill et Reyda sp. n., and two species are formally transferred to the genus, S. amuletum (Butler, 1987) comb. n., and S. cadenati (Euzet, 1954) comb. n., the latter of which is redescribed. The species differ in the configuration of the other bothridial septa and in proglottid anatomy. Species of Stillabothrium were found parasitising a total of 17 species of batoid elasmobranchs of the genera Dasyatis Rafinesque, Glaucostegus Bonaparte, Himantura Müller et Henle, Pastinachus Rüppell, Rhinobatos Linck and Zanobatus Garman, including several host species that are likely new to science. A phylogenetic hypothesis based on Bayesian analysis of 1 084 aligned positions of the D1-D3 region of 28S rDNA for 27 specimens representing 10 species of Stillabothrium and two outgroup species supported the monophyly of Stillabothrium. These results also supported morphologically determined species boundaries in all cases in which more than one specimen of a putative species was included in the analysis. Host specificity appears to vary across species of Stillabothrium, with the number of host species parasitised by each species of Stillabothrium ranging from one to four. The geographic distribution of species of Stillabothrium spans the eastern Hemisphere, including the eastern Atlantic (coastal Senegal) and several locations in the Indo-Pacific (coastal Vietnam, Borneo and Australia). In addition, Phyllobothrium biacetabulatum Yamaguti, 1960 is formally transferred into family Escherbothriidae, although its generic placement remains uncertain (species incertae sedis).

High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse.

Macrophage infection is considered to play an important role in HIV-1 pathogenesis and persistence. Using a primary cell-based coculture model, we show that monocyte-derived macrophages (MDM) efficiently transmit a high-multiplicity HIV-1 infection to autologous CD4(+) T cells through a viral envelope glycoprotein (Env) receptor- and actin-dependent virological synapse (VS), facilitated by interactions between ICAM-1 and LFA-1. Virological synapse (VS)-mediated transmission by MDM results in high levels of T cell HIV-1 integration and is 1 to 2 orders of magnitude more efficient than cell-free infection. This mode of cell-to-cell transmission is broadly susceptible to the activity of CD4 binding site (CD4bs) and glycan or glycopeptide epitope-specific broadly neutralizing monoclonal antibodies (bNMAbs) but shows resistance to bNMAbs targeting the Env gp41 subunit membrane-proximal external region (MPER). These data define for the first time the structure and function of the macrophage-to-T cell VS and have important implications for bNMAb activity in HIV-1 prophylaxis and therapy. IMPORTANCE The ability of HIV-1 to move directly between contacting immune cells allows efficient viral dissemination with the potential to evade antibody attack. Here, we show that HIV-1 spreads from infected macrophages to T cells via a structure called a virological synapse that maintains extended contact between the two cell types, allowing transfer of multiple infectious events to the T cell. This process allows the virus to avoid neutralization by a class of antibody targeting the gp41 subunit of the envelope glycoproteins. These results have implications for viral spread in vivo and the specificities of neutralizing antibody elicited by antibody-based vaccines.

Close to me: enhancing kangaroo care practice for NICU staff and parents.

PURPOSE: The benefits of kangaroo care (KC) are well supported by previously published studies, yet KC is offered inconsistently and faces obstacles in the neonatal intensive care unit (NICU). The March of Dimes designed Close to Me to facilitate and increase KC in NICUs. The program incorporates KC education for nurses and parents, as well as awareness and comfort components. The purpose of this study was to assess whether Close to Me increased favorable attitudes toward KC among nurses and parents, and changed nurse and parent behaviors to implement KC earlier, more often and for longer duration. SUBJECTS AND DESIGN: This study took place in 5 NICUs with 48 nurse participants and 101 parent participants. It used a pre-/postprogram implementation design for nurses and a nonequivalent comparison versus intervention group design for parents. METHODS: Nurses and parents were surveyed on knowledge, attitudes, perceived behavioral control, and behavior. Comparisons were made pre- and postprogram implementation for nurses and between intervention and comparison groups for parents. Nurse focus groups were conducted pre- and postimplementation and analyzed using a constant comparative analysis method. Parents recorded care behaviors and satisfaction in journals, which were analyzed similarly. MAIN OUTCOME MEASURES/PRINCIPAL RESULTS: After the Close to Me intervention, nurses reported more positive attitudes toward KC (P = .04), increased transfer of ventilated babies from incubators to parents (P = .01), and more parents requesting KC. Parents who received Close to Me had greater knowledge about KC (P = .03) compared with those who did not. With the Close to Me intervention, all babies born at less than 28 weeks' gestation had KC by the age of 12 days, whereas without the intervention, some did not have KC until the age of 31 days (P < .05). CONCLUSIONS: March of Dimes Close to Me improved knowledge and behavior regarding KC in NICUs. By offering KC education to parents, providing KC awareness and comfort components, and providing information and encouragement on the benefits and feasibility of KC to nurses, hospitals can potentially promote earlier and more frequent use of KC, particularly with infants born less than 28 weeks' gestation.

A collaborative approach to designing an online nutrition education program for people with multiple sclerosis.

PURPOSE: People with multiple sclerosis (pwMS) want disease-specific dietary advice to reduce the confusion around diet. This study used co-design principles to develop an online nutrition education program for pwMS. METHODS: Mixed-methods (multiphase sequential design). Phase 1: online survey (n = 114 pwMS) to explore preferred content and characteristics of a nutrition program and develop a draft program. Phase 2: feedback on the draft program from stakeholders (two meetings; n = 10 pwMS and multiple sclerosis (MS) health professionals) and pwMS (two workshops; n = 6) to produce a full program prototype. Phase 3: cognitive interviews (n = 8 pwMS plus 1 spouse) to explore acceptability and ease of comprehension of one module of the program, analysed using deductive content analysis. RESULTS: Preferred topics were included in the program, which were further developed with consumer feedback. Cognitive interviews produced four themes: (1) positive and targeted messaging to motivate behaviour change; (2) "not enough evidence" is not good enough; (3) expert advice builds in credibility; and (4) engaging and appropriate online design elements are crucial. CONCLUSIONS: Positive language appears to improve motivation to make healthy dietary changes and engagement with evidence-based nutrition resources. To ensure acceptability, health professionals can use co-design to engage consumers when developing resources for pwMS.IMPLICATIONS FOR REHABILITATIONCo-designed nutrition education programs can help people achieve high-quality diets in line with recommendations, but very few programs exist for people with multiple sclerosis (MS), and none were co-designedThe participatory research in this study was instrumental in ensuring that important information regarding program acceptability was identifiedCo-design can ensure that the language is appropriate for the target audience, and positive language appeared to improve motivation in people with MS to engage with the online nutrition education programWhere practical and feasible, health professionals should collaborate with MS consumers when developing resources, and use positive, empowering language.

Community infant safe sleep and breastfeeding promotion and population level-outcomes: A mixed methods study.

PROBLEM: In the U.S., sudden unexpected infant deaths due to accidental suffocation and strangulation in bed are increasing. Though breastfeeding is a protective factor against sudden unexpected infant death, motivations to breastfeed often couple with unsafe infant sleep practices. Racial/ethnic disparities are present in sudden unexpected infant death, accidental suffocation and strangulation in bed, and breastfeeding. BACKGROUND: Promoting infant safe sleep and breastfeeding through community-level initiatives could address disparities in related outcomes. AIM: Investigate the relationship between community-level strategies and associated state-level outcomes for infant safe sleep and breastfeeding. METHODS: We employed an intervention mixed methods framework and exploratory sequential design. The qualitative component entailed a hermeneutical phenomenological framework to analyze key informant interview data from seven U.S. community-level providers participating in a practice improvement initiative. The quantitative component entailed descriptively analyzing infant safe sleep and breastfeeding indicators from the 2019 Pregnancy Risk Assessment Monitoring System and Ohio Pregnancy Assessment Survey. Qualitative and quantitative data were linked through embedded integration. FINDINGS: We identified two mixed insights: gaps in promotion and outcomes, and persistent disparities between infant safe sleep and breastfeeding promotion and outcomes. DISCUSSION: Our findings indicate conversational approaches could improve infant safe sleep and breastfeeding promotion, outcomes, and relative disparities. We find that community collaboration is needed to address organizational capacity limitations in promoting infant safe sleep and breastfeeding. CONCLUSION: Community-level organizations and providers should consider tailoring program offerings and care delivery to include conversational approaches and community collaboration to promote infant safe sleep and breastfeeding and decrease relative disparities in outcomes.

Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis.

Efferocytic clearance of apoptotic cells in general, and T cells in particular, is required for tissue and immune homeostasis. Transmembrane mucins are extended glycoproteins highly expressed in the cell glycocalyx that function as a barrier to phagocytosis. Whether and how mucins may be regulated during cell death to facilitate efferocytic corpse clearance is not well understood. Here we show that normal and transformed human T cells express a subset of mucins which are rapidly and selectively removed from the cell surface during apoptosis. This process is mediated by the ADAM10 sheddase, the activity of which is associated with XKR8-catalyzed flipping of phosphatidylserine to the outer leaflet of the plasma membrane. Mucin clearance enhances uptake of apoptotic T cells by macrophages, confirming mucins as an enzymatically-modulatable barrier to efferocytosis. Together these findings demonstrate a glycocalyx regulatory pathway with implications for therapeutic intervention in the clearance of normal and transformed apoptotic T cells.