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We present a genome assembly from an individual male specimen of Plusia festucae (Gold Spot; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence has a total length of 422.50 megabases. Most of the assembly (99.92%) is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.3 kilobases in length. Gene annotation of this assembly on Ensembl identified 19,273 protein-coding genes.

To explore the narrowing of the concept of ‘global’ in global health, this article traces how Latin America has held a place of both privilege and power as well as marginalisation in the field. We employ a modified extended case method to examine how Latin America has been ‘seen’ and ‘heard’ in understandings of global health, underscoring the region’s shifting role as a key site for research and practice in ‘tropical medicine’ from the mid-nineteenth century through World War II, to a major player and recipient of development assistance throughout the ‘international health’ era after World War II until the late twentieth century, to a region progressively marginalised within ‘global health’ since the mid-1980s/1990s. We argue that the progressive marginalisation of Latin America and Southern theory has not only hurt health equity and services, but also demonstrates the fundamental flaws in contemporary ‘global’ thinking. The narrowing of global health constitutes coloniality of power, with Northern institutions largely defining priority regions and epistemic approaches to health globally, thus impoverishing the field from the intellectual resources, political experience, and wisdom of Latin America’s long traditions of social medicine and collective health.

This editorial summarises the papers selected for publication in the Special Issue on Advances in Volt/Var Control for Active Distribution Networks with High-Level Intermittent Renewable Energy Resources. The Special Issue contains 13 high-quality papers which are classified into novel models of VVC (3 papers), design of VVC framework (3 papers), data-driven VVC (5 papers), and VVC in special power systems (2 papers). The Special Issue can provide advanced VVC methods with invaluable insights to enhance renewable energy utilisation efficiency, power loss reduction for public infrastructure, and guarantee high power quality for end-users.

Here we describe the use of a synthetic polyurethane matrix in the setting of burns and other complex wounds in the largest United States case series to date. A retrospective review was conducted at a verified, regional burn center. All patients greater than 18 years of age who received this matrix between January 2019 and July 2023 were included. A total of 182 patients with 250 wounds were included in this study. Thirty-seven percent were smokers, 23.6 % had diabetes and 5.5 % had peripheral vascular disease. The majority were acute burn wounds (60 %), followed by trauma (24.4 %), chronic wounds (5.6 %), infection (4 %) and donor sites (2 %). Exposed structures included fat (54 %), muscle (30 %), bone (16 %) and tendon (14.4 %). Microbial colonization was present in 143 (57.2 %) of cases: 98 (39.2 %) pre-application and 89 (35.6 %) post application. The incidence of new microbial colonisation post-application was 25.6 %. Infection was present in 117 (46.8 %) cases, 49 (19.6 %) pre-matrix application, 44 (17.6 %) post-matrix application and 24 (9.6 %) pre and post application. Eighteen patients (10 %) died. Median length of stay was 27 days. Median time to matrix implantation was 10 days. Median time from matrix placement to skin grafting was 35 days. Where documented, there were 162 wounds (83.5 %) with > 95 % matrix survival and 136 wounds (82.4 %) with > 95 % skin graft survival even in the setting of adverse factors such as infection, diabetes, or nicotine use. This study demonstrates the robustness of this skin substitute to achieve successful reconstruction even in the setting of adverse patient or wound characteristics.

Abstract Background Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. Methods We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. Results The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. Conclusions VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

Quantum well infrared photodetectors (QWIPs) have been demonstrated to be a suitable candidate for IR detection applications. These detectors attracted increasing interest due to their design flexibility and broad spectral absorption from short wave (SWIR) to long wave infrared (LWIR) and high uniformity. In this paper, we demonstrate device design, growth, and characterization of a p-type AlxGa1-xN/GaN quantum well infrared photodetector (QWIP) for near IR absorption with 1.55 μm peak grown by metal organic chemical vapor deposition (MOCVD). Utilizing a p-QWIP allows for normal incidence light absorption due to the strong band mixing between heavy and light holes at k ≠ 0 which eliminates the need for light couplers such as grating and facilitates the fabrication of large focal plane arrays (FPAs). We developed MOCVD growth conditions to achieve nm-thick and smooth interfaces in QWIP. Sample characterizations including atomic force microscopy (AFM) show uniform surface morphology with RMS roughness ∼0.5 nm. Scanning transmission electron microscopy (STEM) was used to characterize layer thicknesses and interface roughness. We demonstrate energy band diagram simulation of an AlxGa1-xN/GaN p-QWIP by considering polarization chargers to determine the accurate band offset and adjust the absorption wavelength (ISBT energies). Our results show the feasibility of MOCVD-grown p-type AlxGa1-xN/GaN QWIP for IR absorption and open a pathway for further research and growth development on III-Nitride p-QWIPs, allowing growth and fabrication of large focal plane arrays.

Psoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body’s immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients’ quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials.

Introduction: Bone tumors, characterized by diverse locations and shapes, often necessitate surgical excision followed by custom implant placement to facilitate targeted bone reconstruction. Leveraging additive manufacturing, patient-specific implants can be precisely tailored with complex geometries and desired stiffness, enhancing their suitability for bone ingrowth.Methods: In this work, a finite element model is employed to assess patient-specific lattice implants in femur bones. Our model is validated using experimental data obtained from an animal study (n = 9).Results: The results demonstrate the accuracy of the proposed finite element model in predicting the implant mechanical behavior. The model was used to investigate the influence of reducing the elastic modulus of a solid Ti6Al4V implant by tenfold, revealing that such a reduction had no significant impact on bone behavior under maximum compression and torsion loading. This finding suggests a potential avenue for reducing the endoprosthesis modulus without compromising bone integrity.Discussion: Our research suggests that employing fully lattice implants not only facilitates bone ingrowth but also has the potential to reduce overall implant stiffness. This reduction is crucial in preventing significant bone remodeling associated with stress shielding, a challenge often associated with the high stiffness of fully solid implants. The study highlights the mechanical benefits of utilizing lattice structures in implant design for enhanced patient outcomes.

Scope2´-Fucosyllactose (2´-FL), the most abundant oligosaccharide in human milk, plays an important role in numerous biological functions, including improved learning. It is not clear, however, whether 2´-FL or a cleavage product could influence neuronal cell activity. Thus, we investigated the effects of 2´-FL, its monosaccharide fucose (Fuc), and microbial fermented 2´-FL and Fuc on the parameters of neuronal cell activity in an intestinal–neuronal transwell co-culture system in vitro.MethodsNative 13C-labeled 2´-FL and 13C-Fuc or their metabolites, fermented with Bifidobacterium (B.) longum ssp. infantis and B. breve, which were taken from the lag-, log- and stationary (stat-) growth phases of batch cultures, were applied to the apical compartment of the co-culture system with Caco-2 cells representing the intestinal layer and all-trans-retinoic acid-differentiated SH-SY5Y (SH-SY5YATRA) cells mimicking neuronal-like cells. After 3 h of incubation, the culture medium in the basal compartment was monitored for 13C enrichment by using elemental analysis isotope-ratio mass spectrometry (EA-IRMS) and effects on cell viability, plasma, and mitochondrial membrane potential. The neurotransmitter activation (BDNF, GABA, choline, and glutamate) of SH-SY5YATRA cells was also determined. Furthermore, these effects were also measured by the direct application of 13C-2´-FL and 13C-Fuc to SH-SY5YATRA cells.ResultsWhile no effects on neuronal-like cell activities were observed after intact 2´-FL or Fuc was incubated with SH-SY5YATRA cells, supernatants from the stat-growth phase of 2´-FL, fermented by B. longum ssp. infantis alone and together with B. breve, significantly induced BDNF release from SH-SY5YATRA cells. No such effects were found for 2´-FL, Fuc, or their fermentation products from B. breve. The BDNF release occurred from an enhanced vesicular release, which was confirmed by the use of the Ca2+-channel blocker verapamil. Concomitant with this event, 13C enrichment was also observed in the basal compartment when supernatants from the stat-growth phase of fermentation by B. longum ssp. infantis alone or together with B. breve were used.ConclusionThe results obtained in this study suggest that microbial products of 2´-FL rather than the oligosaccharide itself may influence neuronal cell activities.

Abstract Neuroticism is a heritable trait composed of separate facets, each conferring different levels of protection or risk, to health. By examining mitochondrial DNA in 269,506 individuals, we show mitochondrial haplogroups explain 0.07-0.01% of variance in neuroticism and identify five haplogroup and 15 mitochondria-marker associations across a general factor of neuroticism, and two special factors of anxiety/tension, and worry/vulnerability with effect sizes of the same magnitude as autosomal variants. Within-haplogroup genome-wide association studies identified H-haplogroup-specific autosomal effects explaining 1.4% variance of worry/vulnerability. These H-haplogroup-specific autosomal effects show a pleiotropic relationship with cognitive, physical and mental health that differs from that found when assessing autosomal effects across haplogroups. We identify interactions between chromosome 9 regions and mitochondrial haplogroups at P

Microdroplet resonators provide an excellent tool for optical studies of water, but water microdroplets are difficult to maintain outside a carefully controlled environment. We present a method for maintaining a water microdroplet resonator on a 3D-printed hydrophobic surface in an ambient environment. The droplet is maintained through a passive microfluidic system that supplies water to the droplet through a vertical channel at a rate equivalent to its evaporation. In this manner, we are able to create and passively maintain water microdroplet resonators with quality factors as high as 3×108.

Cognitive impairments are a key feature of psychopathology. Here, authors exploit the genetic overlap between cognitive dimensions and psychopathology to parse the biology of psychiatric illness and identify “meta-loci” genome segments characterized by specific patterns of overlap.

Background: Young people’s gambling behaviours are associated with a range of individual, interpersonal and community factors. This study explored the association between exposure to types of gambling advertising and promotions and adolescent gambling behaviours. Methods: Students from two states answered gambling questions as part of the 2017 Australian Secondary Students’ Alcohol and Drug (ASSAD) Survey. Students reported gambling behaviours (gambling in the last month, types of gambling activities), exposure to gambling promotions during the last 30 days (e.g. ads for gambling on TV, online, live studio crosses), and were assessed for problem gambling. Principal Component Analysis suggested four groups of gambling promotion exposure. Logistic regression analyses examined the association between gambling promotion exposure and student gambling, engagement in hard gambling activities in the last month, and problem or at risk gambling, controlling for a range of student characteristics. Results: Most students (81%) had been exposed to some form of gambling promotion or advertisement in the last month, most commonly TV, social media and sporting event advertisements. Exposure to online gambling ads (including websites, pop-ups on websites, and social media) in the last month was significantly associated with gambling in the last month, and being classified as an at risk or problem gambler; but not with participating in hard gambling activities. After adjusting for exposure to gambling advertising across categories, no other advertising exposure types were associated with adolescent gambling behaviours. Conclusions: Study findings point to the need to impose restrictions on gambling advertisements and promotions, particularly those presented online.

Abstract BackgroundCollagenase Clostridium histolyticum ObjectivesThe article provides an overview of cellulite treatment with CCH-aaes, including patient identification and education, treatment planning, CCH-aaes dilution, injection technique, safety, and early experience with mitigation of adverse events, including bruising. MethodsAs part of a continuing medical education (CME; xMedica, Alpharetta, GA) event on developments in cellulite treatment, a panel of experts developed a course and roundtable, which included lectures on cellulite physiology, new developments in the field of cellulite treatment, demonstrations of injection technique for CCH-aaes, and a review of considerations for the use of CCH-aaes in real-world clinical practice. ResultsThe practical guidance presented here is based upon real-world experience with CCH-aaes. The discussion includes strategies based on early experience for how to obtain the best results as well as suggestions on how to mitigate bruising. ConclusionsCCH-aaes has been a welcome addition to the armamentarium for the treatment of cellulite. With knowledge of proper patient evaluation and injection technique, thorough patient education, diligent photography, and developing research on bruising mitigation, CCH-aaes shows great promise as an effective and safe modality for the management of cellulite. Level of Evidence: 5

Abstract Background Exchanging experiences of patient and public involvement (PPI) can bring insights into why, how and when PPI is most effective. The aim of this study was to explore the experiences of patient research partners (PRPs) and researchers engaged in a co-creative long-term collaboration in cancer research. Methods The aim and procedures of this study were jointly decided upon by PRPs and researchers. The PRPs included former patients treated for cancer and significant others of the same target group. The participants (11 PRPs, 6 researchers) took part in semi-structured telephone interviews. The interviews were analysed using qualitative content analysis by a researcher who had no prior relationships with the participants. Results Five overarching categories were identified: Reasons for investing in a long-term collaboration, Benefits of participating, Improving the research, Elements of success and Challenges and ways to improve. Reasons for investing in the collaboration included the desire to improve cancer care and to make use of own negative experiences. Benefits of participating included a positive impact on the PRPs’ psychosocial adjustment to the illness. Moreover, the researchers highlighted that working together with the PRPs made the research feel more meaningful. The participants reported that the collaboration improved the relevance and acceptability of the research. Having a shared goal, a clear but yet accommodating structure, as well as an open and trustful working atmosphere were recognised as elements of success. The PRPs furthermore emphasized the importance of seeing that their input mattered. Among the few challenges raised were the distance to the meeting venues for some PRPs and a limited diversity among participants. Conclusions This study identified factors essential to researchers and clinicians attempting to engage the public in research. Our results suggest that for successful patient involvement, the purpose and format of the collaboration should be clear to both PRPs and researchers. A clear but yet accommodating structure and keen leadership emerged as key factors to create a sense of stability and a trustful atmosphere. Furthermore, providing regular feedback on how PRPs input is implemented is important for PRPs to stay committed over time.

Abstract Background Exercise is recommended in guidelines for asthma management and has beneficial effects on symptom control, inflammation and lung function in patients with sub-optimally controlled asthma. Despite this, physical activity levels in patients with difficult asthma are often impaired. Understanding the barriers to exercise in people with difficult asthma is crucial for increasing their activity, and in implementing successful, disease modifying, and holistic approaches to improve their health. Methods 62 Patients within the WATCH Difficult Asthma Cohort (Southampton, UK) completed an Exercise Therapy Burden Questionnaire (ETBQ). The results were analyzed with contemporaneous asthma-related data to determine relationships between perceived exercise barriers and asthma and comorbidity characteristics Results Patients were reflective of a difficult asthma cohort, 66% were female, and 63% were atopic. They had a high BMI (median [inter-quartile range]) of 29.3 [25.5–36.2], age of 53.5 [38.75, 65.25], impaired spirometry with FEV1 73% predicted [59.5, 86.6%] and FEV/FVC ratio of 72 [56.5, 78.0] and poor symptom control, as defined by an Asthma Control Questionnaire (ACQ6) result of 2.4 [1.28, 3.2]. A high perceived barriers to exercise score was significantly correlated with increased asthma symptoms (r = 0.452, p

Depression is correlated with many brain-related traits. Here, Shen et al. perform phenome-wide association studies of a depression polygenic risk score (PRS) and find associations with 51 behavioural and 26 neuroimaging traits which are further followed up on using Mendelian randomization and mediation analyses.

Background: Venezuelan migration is the second largest international displacement in contemporary history. Yet, amid global calls for the inclusion of migrants and refugees in COVID-19 vaccination priority groups, little is known about how Latin American countries are prioritising COVID-19 vaccination for Venezuelans. This rapid scoping review addresses this gap, taking up a Latin American Social Medicine approach to assess the region's sociopolitical context and explore the extent to which Venezuelan migrants are considered in COVID-19 vaccination strategies in Latin America. Methods: We conducted a three-phased rapid scoping review assessing peer-reviewed literature, gray literature, and government documents addressing COVID-19 vaccine access for displaced Venezuelans in Latin America. Documents published in English, Spanish, or Portuguese between January 2020 and June 2021 were included. Peer-reviewed literature search yielded 142 results and 13 articles included in the analysis; Gray literature screening resulted in 68 publications for full-text review and 37 were included; and official Ministry of Health policies in Argentina, Brazil, Chile, Colombia, Ecuador, and Peru were reviewed in-depth. Screening and data extraction used a combination of online platforms (Covidence, Google Forms, Zotero, and Excel) and the team met twice weekly to review, compare, discuss, analyse, and interpret data across a 6-week period. Findings: Findings from country-level policies revealed a heterogeneous and shifting policy landscape amid the COVID-19 pandemic, which strongly juxtaposed calls for a rights-based, social justice approach to COVID-19 vaccination evidenced in the peer-reviewed and gray literature. For example, under extreme resource constraints resulting from a chronically underfunded health system and mass Venezuelan migration. Colombia's vaccination plan excluded migrants with irregular migration status. Countries prioritised COVID-19 vaccines to certain “at-risk” groups defined by individual epidemiological factors rather than social vulnerability, limiting vaccine access for displaced Venezuelans in the region. Country-level policies differentiated, at times arbitrarily, between refugees, irregular migrants, and regular migrants, with important implications for vaccine access. While international right to health legislation prohibits discrimination based on migration status and urges states to refrain from denying access to preventive health services, these results suggest the need for further guidance on terminology to better contend with migrants' social vulnerabilities. Interpretation: COVID-19 is rapidly evolving and there is an urgent need for rights-based approaches to vaccination that consider sociopolitical contexts, especially impacts of mass migration. Findings underscore the need to better integrate Venezuelan migrants into vaccination strategies, not only as a matter of social justice, but a pragmatic public health strategy. Funding: Funding provided by the Canadian Social Sciences and Humanities Research Council Insight Development Grant.

Ecosystem markets are proliferating around the world in response to increasing demand for climate change mitigation and provision of other public goods. However, this may lead to perverse outcomes, for example where public funding crowds out private investment or different schemes create trade-offs between the ecosystem services they each target. The integration of ecosystem markets could address some of these issues but to date there have been few attempts to do this, and there is limited understanding of either the opportunities or barriers to such integration. This paper reports on a comparative analysis of eleven ecosystem markets in operation or close to market in Europe, based on qualitative analysis of 25 interviews, scheme documentation and two focus groups. Our results indicate three distinct types of markets operating from the regional to national scale, with different modes of operation, funding and outcomes: regional ecosystem markets, national carbon markets and green finance. The typology provides new insights into the operation of ecosystem markets in practice, which may challenge traditionally held notions of Payment for Ecosystem Services. Regional ecosystem markets, in particular, represent a departure from traditional models, by using a risk-based funding model and aggregating both supply and demand to overcome issues of free-riding, ecosystem service trade-offs and land manager engagement. Central to all types of market were trusted intermediaries, brokers and platforms to aggregate supply and demand, build trust and lower transaction costs. The paper outlines six options for blending public and private funding for the provision of ecosystem services and proposes a framework for integrating national carbon markets and green finance with regional ecosystem markets. Such integration may significantly increase funding for regenerative agriculture and conservation across multiple habitats and services, whilst addressing issues of additionality and ecosystem service trade-offs between multiple schemes.

Pregravid obesity is one of the major risk factors for pregnancy complications such as gestational diabetes mellitus (GDM) and an increased risk of cardiovascular events in children of affected mothers. However, the biological mechanisms that underpin these adverse outcomes are not well understood. High-density lipoproteins (HDLs) are antiatherogenic by promoting the efflux of cholesterol from macrophages and by suppression of inflammation. Functional impairment of HDLs in obese and GDM-complicated pregnancies may have long-term effects on maternal and offspring health. In the present study, we assessed metrics of HDL function in sera of pregnant women with overweight/obesity of the DALI lifestyle trial (prepregnancy BMI ≥ 29 kg/m2) and women with normal weight (prepregnancy BMI < 25 kg/m2), as well as HDL functionalities in cord blood at delivery. We observed that pregravid obesity was associated with impaired serum antioxidative capacity and lecithin–cholesterol acyltransferase activity in both mothers and offspring, whereas maternal HDL cholesterol efflux capacity was increased. Interestingly, functionalities of maternal and fetal HDL correlated robustly. GDM did not significantly further alter the parameters of HDL function and metabolism in women with obesity, so obesity itself appears to have a major impact on HDL functionality in mothers and their offspring.

Gestational hypertension (GHTN) is associated with an increased cardiovascular risk for mothers and their offspring later in life. High-density lipoproteins (HDL) are anti-atherogenic by promoting efflux of cholesterol from macrophages and suppression of endothelial cell activation. Functional impairment of HDL in GHTN-complicated pregnancies may affect long-term health of both mothers and offspring. We studied functional parameters of maternal and neonatal HDL in 192 obese women (pre-pregnancy BMI ≥ 29), who were at high risk for GHTN. Maternal blood samples were collected longitudinally at

Household income is used as a marker of socioeconomic position, a trait that is associated with better physical and mental health. Here, Hill et al. report a genome-wide association study for household income in the UK and explore its relationship with intelligence in post-GWAS analyses including Mendelian randomization.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Introduction: The entangled health and economic crises fueled by COVID-19 have exacerbated the challenges facing Venezuelan migrants. There are more than 5.6 million Venezuelan migrants globally and almost 80% reside throughout Latin America. Given the growing number of Venezuelan migrants and COVID-19 vulnerability, this rapid scoping review examined how Venezuelan migrants are considered in Latin American COVID-19 vaccination strategies. Material and Methods: We conducted a three-phased rapid scoping review of documents published until June 18, 2021: Peer-reviewed literature search yielded 142 results and 13 articles included in analysis; Gray literature screen resulted in 68 publications for full-text review and 37 were included; and official Ministry of Health policies in Argentina, Brazil, Chile, Colombia, Ecuador, and Peru were reviewed. Guided by Latin American Social Medicine (LASM) approach, our analysis situates national COVID-19 vaccination policies within broader understandings of health and disease as affected by social and political conditions. Results: Results revealed a heterogeneous and shifting policy landscape amid the COVID-19 pandemic which strongly juxtaposed calls to action evidenced in literature. Factors limiting COVID-19 vaccine access included: tensions around terminologies; ambiguous national and regional vaccine policies; and pervasive stigmatization of migrants. Conclusions: Findings presented underscore the extreme complexity and associated variability of providing access to COVID-19 vaccines for Venezuelan migrants across Latin America. By querying the timely question of how migrants and specifically Venezuelan migrants access vaccinations findings contribute to efforts to both more equitably respond to COVID-19 and prepare for future pandemics in the context of displaced populations. These are intersectional and evolving crises and attention must also be drawn to the magnitude of Venezuelan mass migration and the devastating impact of COVID-19 in the region. Integration of Venezuelan migrants into Latin American vaccination strategies is not only a matter of social justice, but also a pragmatic public health strategy necessary to stop COVID-19.

Summary: During development, the mammary gland undergoes extensive remodeling driven by stem cells. Breast cancers are also hierarchically organized and driven by cancer stem cells characterized by CD44+CD24low/− or aldehyde dehydrogenase (ALDH) expression. These markers identify mesenchymal and epithelial populations both capable of tumor initiation. Less is known about these populations in non-cancerous mammary glands. From RNA sequencing, ALDH+ and ALDH−CD44+CD24− human mammary cells have epithelial-like and mesenchymal-like characteristics, respectively, with some co-expressing ALDH+ and CD44+CD24− by flow cytometry. At the single-cell level, these cells have the greatest mammosphere-forming capacity and express high levels of stemness and epithelial-to-mesenchymal transition-associated genes including ID1, SOX2, TWIST1, and ZEB2. We further identify single ALDH+ cells with a hybrid epithelial/mesenchymal phenotype that express genes associated with aggressive triple-negative breast cancers. These results highlight single-cell analyses to characterize tissue heterogeneity, even in marker-enriched populations, and identify genes and pathways that define this heterogeneity. : In this article, Colacino and colleagues use flow-cytometry-sorted populations and single-cell analyses to investigate human mammary stem cells. They discover unexpected phenotypic and functional heterogeneity at the single-cell level, including a subpopulation of ALDH+ stem cells with a hybrid epithelial/mesenchymal phenotype and triple-negative breast cancer-like gene expression pattern. Keywords: breast stem cell, single-cell RNA, epithelial, mesenchymal, hybrid, RNA-seq

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Abstract Background Gestational diabetes mellitus (GDM) is associated with perinatal health risks to both mother and offspring, and represents a large economic burden. The DALI study is a multicenter randomized controlled trial, undertaken to add to the knowledge base on the effectiveness of interventions for pregnant women at increased risk for GDM. The purpose of this study was to evaluate the cost-effectiveness of the healthy eating and/or physical activity promotion intervention compared to usual care among pregnant women at increased risk of GDM from a societal perspective. Methods An economic evaluation was performed alongside a European multicenter-randomized controlled trial. A total of 435 pregnant women at increased risk of GDM in primary and secondary care settings in nine European countries, were recruited and randomly allocated to a healthy eating and physical activity promotion intervention (HE + PA intervention), a healthy eating promotion intervention (HE intervention), or a physical activity promotion intervention (PA intervention). Main outcome measures were gestational weight gain, fasting glucose, insulin resistance (HOMA-IR), quality adjusted life years (QALYs), and societal costs. Results Between-group total cost and effect differences were not significant, besides significantly less gestational weight gain in the HE + PA group compared with the usual care group at 35–37 weeks (−2.3;95%CI:-3.7;-0.9). Cost-effectiveness acceptability curves indicated that the HE + PA intervention was the preferred intervention strategy. At 35–37 weeks, it depends on the decision-makers’ willingness to pay per kilogram reduction in gestational weight gain whether the HE + PA intervention is cost-effective for gestational weight gain, whereas it was not cost-effective for fasting glucose and HOMA-IR. After delivery, the HE + PA intervention was cost-effective for QALYs, which was predominantly caused by a large reduction in delivery-related costs. Conclusions Healthy eating and physical activity promotion was found to be the preferred strategy for limiting gestational weight gain. As this intervention was cost-effective for QALYs after delivery, this study lends support for broad implementation. Trial registration ISRCTN ISRCTN70595832. Registered 2 December 2011.

Abstract Background Depression during pregnancy is associated with higher maternal morbidity and mortality, and subsequent possible adverse effects on the cognitive, emotional and behavioral development of the child. The aim of the study was to identify maternal characteristics associated with poor mental health, in a group of overweight/obese pregnant women in nine European countries, and thus, to contribute to better recognition and intervention for maternal depression. Methods In this cross-sectional observational study, baseline data from early pregnancy (< 20 weeks) of the DALI (Vitamin D and Lifestyle Intervention for gestational diabetes mellitus prevention) study were analyzed. Maternal mental health was assessed with the World Health Organization Well-Being Index (WHO–5). Women were classified as having a low (WHO–5 ≤ 50) or high wellbeing. Results. A total of 735 pregnant women were included. The prevalence of having a low wellbeing was 27.2%, 95% CI [24.0, 30.4]. Multivariate analysis showed independent associations between low wellbeing and European ethnicity, OR = .44, 95% CI [.25, .77], shift work, OR = 1.81, 95% CI [1.11, 2.93], insufficient sleep, OR = 3.30, 95% CI [1.96, 5.55], self-efficacy, OR = .95, 95% CI [.92, .98], social support, OR = .94, 95% CI [.90, .99], and pregnancy-related worries (socioeconomic: OR = 1.08, 95% CI [1.02, 1.15]; health: OR = 1.06, 95% CI [1.01, 1.11]; relationship: OR = 1.17, 95% CI [1.05, 1.31]). Conclusions Mental health problems are common in European overweight/obese pregnant women. The identified correlates might help in early recognition and subsequent treatment of poor mental health problems during pregnancy. This is important to reduce the unfavorable effects of poor mental health on pregnancy outcomes. Trial registration ISRCTN70595832 , 02.12.2011.

Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice. We identified many Arc-interacting proteins, of which PSD95 was the most abundant. PSD95 was essential for Arc assembly into 1.5-MDa complexes and activity-dependent recruitment to excitatory synapses. Integrating human genetic data with proteomic data showed that Arc-PSD95 complexes are enriched in schizophrenia, intellectual disability, autism, and epilepsy mutations and normal variants in intelligence. We propose that Arc-PSD95 postsynaptic complexes potentially affect human cognitive function.

Abstract Background Process evaluation is an essential part of designing and assessing complex interventions. The vitamin D and lifestyle intervention study (DALI) study is testing different strategies to prevent development of gestational diabetes mellitus among European obese pregnant women with a body mass index ≥29 kg/m2. The intervention includes guidance on physical activity and/or healthy eating by a lifestyle coach trained in motivational interviewing (MI). The aim of this study was to assess the process elements: reach, dose delivered, fidelity and satisfaction and to investigate whether these process elements were associated with changes in gestational weight gain (GWG). Methods Data on reach, dose delivered, fidelity, and satisfaction among 144 participants were collected. Weekly recruitment reports, notes from meetings, coach logs and evaluation questionnaires (n = 110) were consulted. Fidelity of eight (out of twelve) lifestyle coach practitioners was assessed by analysing audio recorded counselling sessions using the MI treatment integrity scale. Furthermore, associations between process elements and GWG were assessed with linear regression analyses. Results A total of 20% of the possible study population (reach) was included in this analysis. On average 4.0 (of the intended 5) face-to-face sessions were delivered. Mean MI fidelity almost reached ‘expert opinion’ threshold for the global scores, but was below ‘beginning proficiency’ for the behavioural counts. High variability in quality of MI between practitioners was identified. Participants were highly satisfied with the intervention, the lifestyle coach and the intervention materials. No significant associations were found between process elements and GWG. Conclusion Overall, the intervention was well delivered and received by the study population, but did not comply with all the principles of MI. Ensuring audio recording of lifestyle sessions throughout the study would facilitate provision of individualized feedback to improve MI skills. A larger sample size is needed to confirm the lack of association between process elements and GWG. Trial registration ISRCTN registry: ISRCTN70595832 ; Registered 12 December 2011.

Abstract We investigated the biomechanical relationship between intraluminal pressure within small mesenteric resistance arteries, oxidant activation of PKG, Ca2+ sparks, and BK channel vasoregulation. Mesenteric resistance arteries from wild type (WT) and genetically modified mice with PKG resistance to oxidative activation were studied using wire and pressure myography. Ca2+ sparks and Ca2+ transients within vascular smooth muscle cells of intact arteries were characterized using high‐speed confocal microscopy of intact arteries. Arteries were studied under conditions of varying intraluminal pressure and oxidation. Intraluminal pressure specifically, rather than the generic stretch of the artery, was necessary to activate the oxidative pathway. We demonstrated a graded step activation profile for the generation of Ca2+ sparks and also a functional “ceiling” for this pressure –‐sensitive oxidative pathway. During steady state pressure ‐ induced constriction, any additional Ca2+ sensitive‐K+ channel functional availability was independent of oxidant activated PKG. There was an increase in the amplitude, but not the Area under the Curve (AUC) of the caffeine‐induced Ca2+ transient in pressurized arteries from mice with oxidant‐resistant PKG compared with wild type. Overall, we surmise that intraluminal pressure within resistance arteries controls Ca2+ spark vasoregulation through a tightly controlled pathway with a graded onset switch. The pathway, underpinned by oxidant activation of PKG, cannot be further boosted by additional pressure or oxidation once active. We propose that these restrictive characteristics of pressure‐induced Ca2+ spark vasoregulation confer stability for the artery in order to provide a constant flow independent of additional pressure fluctuations or exogenous oxidants.

Intelligence and education are predictive of better physical and mental health, socioeconomic position (SEP), and longevity. However, these associations are insufficient to prove that intelligence and/or education cause these outcomes. Intelligence and education are phenotypically and genetically correlated, which makes it difficult to elucidate causal relationships. We used univariate and multivariable Mendelian randomization to estimate the total and direct effects of intelligence and educational attainment on mental and physical health, measures of socioeconomic position, and longevity. Both intelligence and education had beneficial total effects. Higher intelligence had positive direct effects on income and alcohol consumption, and negative direct effects on moderate and vigorous physical activity. Higher educational attainment had positive direct effects on income, alcohol consumption, and vigorous physical activity, and negative direct effects on smoking, BMI and sedentary behaviour. If the Mendelian randomization assumptions hold, these findings suggest that both intelligence and education affect health.

In 2017, 34.8% of total electricity consumption in Northern Ireland was generated from renewable sources located in Northern Ireland. Alongside other significant changes to the electricity sector this leads to an increasing need for reactive power. This paper provides an overview of NIE Networks' nodal controller project which aims to deliver reactive power support to the wider system through the utilisation of Distributed Energy Resources (DERs). The requirements and implementation of the nodal controller are outlined with future work proposed to provide additional reactive power support to the system.

Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86–92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis.