Global patterns of enhancer activity during sea urchin embryogenesis assessed by eRNA profiling.

We used capped analysis of gene expression with sequencing (CAGE-seq) to profile eRNA expression and enhancer activity during embryogenesis of a model echinoderm: the sea urchin, Strongylocentrotus purpuratus We identified more than 18,000 enhancers that were active in mature oocytes and developing embryos and documented a burst of enhancer activation during cleavage and early blastula stages. We found that a large fraction (73.8%) of all enhancers active during the first 48 h of embryogenesis were hyperaccessible no later than the 128-cell stage and possibly even earlier. Most enhancers were located near gene bodies, and temporal patterns of eRNA expression tended to parallel those of nearby genes. Furthermore, enhancers near lineage-specific genes contained signatures of inputs from developmental gene regulatory networks deployed in those lineages. A large fraction (60%) of sea urchin enhancers previously shown to be active in transgenic reporter assays was associated with eRNA expression. Moreover, a large fraction (50%) of a representative subset of enhancers identified by eRNA profiling drove tissue-specific gene expression in isolation when tested by reporter assays. Our findings provide an atlas of developmental enhancers in a model sea urchin and support the utility of eRNA profiling as a tool for enhancer discovery and regulatory biology. The data generated in this study are available at Echinobase, the public database of information related to echinoderm genomics.

Social determinants of health and sepsis: a case-control study.

PURPOSE: We aimed to identify whether social determinants of health (SDoH) are associated with the development of sepsis and assess the differences between individuals living within systematically disadvantaged neighbourhoods compared with those living outside these neighbourhoods. METHODS: We conducted a single-centre case-control study including 300 randomly selected adult patients (100 patients with sepsis and 200 patients without sepsis) admitted to the emergency department of a large academic tertiary care hospital in Hamilton, ON, Canada. We collected data on demographics and a limited set of SDoH variables, including neighbourhood household income, smoking history, social support, and history of alcohol disorder. We analyzed study data using multivariate logistic regression models. RESULTS: The study included 100 patients with sepsis with a median [interquartile range (IQR)] age of 75 [58-84] yr and 200 patients without sepsis with a median [IQR] age of 72 [60-83] yr. Factors significantly associated with sepsis included arrival by ambulance, absence of a family physician, higher Hamilton Early Warning Score, and a recorded history of dyslipidemia. Important SDoH variables, such as individual or household income and race, were not available in the medical chart. In patients with SDoH available in their medical records, no SDoH was significantly associated with sepsis. Nevertheless, compared with their proportion of the Hamilton population, the rate of sepsis cases and sepsis deaths was approximately two times higher among patients living in systematically disadvantaged neighbourhoods. CONCLUSIONS: This study revealed the lack of available SDoH data in electronic health records. Despite no association between the SDoH variables available and sepsis, we found a higher rate of sepsis cases and sepsis deaths among individuals living in systematically disadvantaged neighbourhoods. Including SDoH in electronic health records is crucial to study their effect on the risk of sepsis and to provide equitable care.

RéSUMé: OBJECTIF: Nous avons cherché à déterminer si les déterminants sociaux de la santé (DSS) étaient associés à l'apparition de sepsis et à évaluer les différences entre les personnes vivant dans des quartiers systématiquement défavorisés et celles vivant à l'extérieur de ces quartiers. MéTHODE: Nous avons mené une étude cas témoins monocentrique portant sur 300 patient·es adultes sélectionné·es au hasard (100 personnes atteintes de sepsis et 200 témoins sans sepsis) admis·es au service des urgences d'un grand hôpital universitaire de soins tertiaires à Hamilton, ON, Canada. Nous avons recueilli des données démographiques et un ensemble limité de variables de DSS, y compris le revenu des ménages du quartier, les antécédents de tabagisme, le soutien social et les antécédents de troubles liés à l'alcool. Nous avons analysé les données de l'étude à l'aide de modèles de régression logistique multivariés. RéSULTATS: L'étude a inclus 100 patient·es atteint·es de sepsis avec un âge médian [écart interquartile (ÉIQ)] de 75 [58-84] ans et 200 patient·es sans sepsis avec un âge médian [ÉIQ] de 72 [60-83] ans. Les facteurs significativement associés au sepsis comprenaient l'arrivée en ambulance, l'absence de médecin de famille, un score Hamilton Early Warning Score plus élevé et des antécédents enregistrés de dyslipidémie. D'importantes variables de DSS, telles que le revenu individuel et du ménage et la race, n'étaient pas disponibles dans le dossier médical. Chez les personnes dont les DSS étaient disponibles dans leur dossier médical, aucun DSS n'était significativement associé au sepsis. Néanmoins, comparativement à leur proportion dans la population de Hamilton, le taux de cas de sepsis et de décès dus au sepsis était environ deux fois plus élevé chez les personnes vivant dans des quartiers systématiquement défavorisés. CONCLUSION: Cette étude a révélé le manque de données disponibles sur les DSS dans les dossiers de santé électroniques. Bien qu'il n'y ait pas d'association entre les variables disponibles et le sepsis, nous avons constaté un taux plus élevé de cas de sepsis et de décès dus à la septicémie chez les personnes vivant dans des quartiers systématiquement défavorisés. L'inclusion des DSS dans les dossiers de santé électroniques est cruciale pour étudier leur effet sur le risque de sepsis et pour dispenser des soins équitables.

Cognitive Aging in Same- and Different-Sex Relationships: Comparing Age of Diagnosis and Rate of Cognitive Decline in the Health and Retirement Study.

INTRODUCTION: The ongoing marginalization of lesbian, gay, and bisexual people has been hypothesized to produce poorer late-in-life cognitive outcomes, according to mechanisms posited by minority stress and allostatic load theories. Yet the existence of those outcomes remains understudied, and results of existing studies have been contradictory. Using a population-based longitudinal aging study, this paper will compare age at diagnosis of Alzheimer's disease (AD) or a related dementia and rates of cognitive decline between participants in same-sex relationships (SSRs) and different-sex relationships (DSRs). METHODS: The study used longitudinal cognitive-health data from the Health and Retirement Study (HRS; 1998-2018; N = 26,344) to analyze the onset of cognitive impairment and AD/dementia and the rates of cognitive change between participants in SSRs and those in DSRs. We hypothesized that SSR participants would have worse overall cognitive functioning in old age and would experience earlier onset of cognitive impairment. Using multiple regression, we compared the ages at which participants in SSRs and DSRs first reported AD or dementia diagnoses and the ages at which they first scored below cutoffs for cognitive impairment, not dementia (CIND) and possible dementia as determined using the cognitive assessment. The study then compared rates of cognitive decline over time across the SSR and DSR groups, including stratified analyses by education, race/ethnicity, wealth, and sex/gender. RESULTS: Participants in SSRs reported dementia diagnoses (ß = -12.346; p = 0.001), crossed the threshold into CIND (ß = -8.815; p < 0.001) and possible dementia (ß = -13.388; p < 0.001) at a younger age than participants in DSRs. When adjusted for covariates, participants in SSRs also had lower cognition at baseline (ß = 0.745; p = 0.003), though having slower rates of cognitive decline when SSR was interacted with time (ß = 0.066; p = 0.003). In separate analyses, cognitive differences for SSR participants were only found in participants without undergraduate degrees, with below-median household incomes, and women. CONCLUSION: Our findings support theories suggesting that marginalization and stigma cause premature cognitive impairment. Findings also suggest that higher education might mitigate the adverse effects of sexuality-minority status on cognitive aging. Results do not support these theories' claims of more rapid cognitive decline; the lower slopes of cognitive decline with time are compatible with the possibility of slower rates of decline for aging individuals in SSRs.

Lipoplasty Combined with Percutaneous Radiofrequency Dermaplasty: A New Strategy for Body Contouring.

BACKGROUND: A new technique in plastic surgery termed percutaneous radiofrequency dermaplasty (PRD) is described. Customized radiofrequency energy is applied via the percutaneous route to produce skin tightening and fascia contraction at body temperature, avoiding thermal injury. We combine PRD with lipoplasty and call this combined procedure dermaplasty-assisted lipoplasty (DAL). The purpose of this study was to review both the safety and efficacy of DAL. METHODS: We developed the required novel device and technique to perform DAL and then performed a clinical trial including Type I and Type II lipodystrophy female patients undergoing a primary liposuction of the circumferential trunk. The trial comprised two phases. In Phase I, 51 patients were included in a prospective, comparative, controlled trial and divided into two groups. In Group 1, 29 patients underwent DAL, and in Group 2, 22 patients underwent a standard suction-assisted lipectomy (SAL) alone. In Phase II, 84 patients underwent DAL, including 9 cases initially scheduled for a mini-abdominoplasty. RESULTS: Phase I: We found better aesthetic results with DAL (93.1%) than with SAL alone (72.7%) [p < .05]. Postoperative correction of flaccid skin was superior with DAL (93.1%) than with SAL alone (36.4%) [p < .01]. Phase II: DAL achieved good-to-excellent aesthetic results in 94% of the cases. CONCLUSIONS: DAL was found to be a reliable and safe treatment for fat removal with concomitant skin and fascia tightening but without compromising the viability of the overlying skin. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Immunogenicity of the CYD tetravalent dengue vaccine using an accelerated schedule: randomised phase II study in US adults.

BACKGROUND: The live attenuated tetravalent dengue vaccine (CYD-TDV) is licensed using a 0-, 6- and 12-month schedule in dengue-endemic areas. An effective shorter schedule may provide more rapid, optimal protection of targeted populations during vaccine campaigns in dengue-endemic countries. We compared immune responses to two schedules of CYD-TDV in a non-endemic population. We also evaluated the impact of yellow fever (YF) co-administration. METHODS: This phase II, open-label, multicentre study enrolled 390 healthy 18-45-year-olds in the USA with no prior exposure to dengue. Participants were randomised (4:4:4:1) to four treatment groups stratified by prior YF vaccine status: Group 1, CYD-TDV standard 0-6-12 months schedule; Group 2, CYD-TDV accelerated 0-2-6 months schedule; Group 3, CYD-TDV accelerated schedule with YF co-administered (dose 1); Group 4, YF vaccination only. Neutralising antibody geometric mean titres (GMTs) and percentages of seropositive participants (antibody titres ≥10 [1/dil]) were measured against each dengue serotype using a 50% plaque reduction neutralisation test. RESULTS: On D28 post-CYD-TDV dose 3, there were no marked differences in seropositivity rates and GMTs between Groups 1 and 2. In Groups 1 and 2 respectively, 73.4 and 82.4% were dengue seropositive for ≥3 serotypes, with 50.0 and 42.6% seropositive against all four serotypes. Flavivirus status (FV+ or FV-) at baseline did not markedly affect GMTs and seropositivity rates with either schedule. In Groups 1 and 2, GMTs measured 6 months after the third dose decreased against all serotypes, except for a small increase in GMT for serotype 4 in Group 1. In addition, dengue seropositivity remained above 70% for serotypes 2, 3 and 4 in Groups 1 and 2. Co-administration with YF did not affect antibody responses against dengue and YF or impact vaccine safety following completion of the compressed schedule, compared to dengue or YF vaccination alone. CONCLUSIONS: The live attenuated CYD-TDV vaccine given in a compressed schedule in a non-endemic setting can elicit similar antibody responses to the licensed CYD-TDV schedule. TRIAL REGISTRATION: This trial was registered on cinicaltrials.gov, NCT01488890 (December 8, 2011).

'Too-much-of-a-good-thing'? The role of advanced eco-learning and contingency factors on the relationship between corporate environmental and financial performance.

Inspired by the natural-resource-based view (NRBV) theory, we attempt to shed light on a controversy which has been persistent over the last decade, concerning the relationship between corporate environmental performance (CEP) and corporate financial performance (CFP). Using the 'too-much-of-a-good-thing' (TMGT) concept, which suggests that "too much can be worse than too little," we link mixed results and consider the roles of advanced eco-learning and contingency factors in influencing the CEP-CFP relationship. Based on a sample composed of ISO 14001 certified companies in Indonesia, and analyzing the data using consistent Partial Least Squares (PLSc), we found that: the CEP-CFP relationship follows an inverted U-shape; advanced eco-learning is a significant predictor of the CEP-CFP relationship, meaning that organizations able to develop higher eco-learning capability will be better able to identify the ideal boundaries of investment in environmental performance without reducing their financial performance; and that contingency factors such as environmental strategy and firm size have a significant role in influencing the CEP-CFP relationship. The study's limitations, implications for practitioners and a future research agenda are also detailed.

Quantification of training load, energy intake, and physiological adaptations during a rugby preseason: a case study from an elite European rugby union squad.

Rugby Union (RU) is a high-speed collision sport consisting of an intermittent activity profile. Given the extreme physical demands of the sport, significant emphasis is placed on players possessing high lean body mass while minimizing body fat. Anecdotally, the most significant changes in body composition are observed during the preseason; however, there are no objective data on the physiological demands and energy intake during this time. We therefore monitored 45 elite European RU players over the 10-week preseason period by assessing training load using Global Positioning System and session rate of perceived exertion (sRPE) while also assessing changes in anthropometry and physical performance. For forwards and backs, respectively, mean weekly distance covered was 9,774 m (1,404) and 11,585 m (1,810) with a total mean weekly sRPE of 3,398 (335) arbitrary units and 2,944 (410) arbitrary units. Mean daily energy intake was 14.8 MJ (1.9) and 13.3 MJ (1.9), carbohydrate (CHO) intake was 3.3 (0.7) and 4.14 (0.4) g·kg body mass, protein intake was 2.52 (0.3) and 2.59 (0.6) g·kg body mass, and fat intake was 1.0 (0.3) and 0.95 (0.3) g·kg body mass for forwards and backs, respectively. Markers of physical performance (1 repetition maximum strength, speed, and repeated sprint tests) and anthropometry (body fat and estimated lean mass) improved in all players. Interestingly, all players self-selected a "low" CHO "high" protein diet. Based on physiological improvements the training load and energy intake seems appropriate, although further research is required to evaluate if such energy intakes would also be suitable for match day performance.

Investigational lymphatic imaging at the bedside in a pediatric postoperative chylothorax patient.

Chylothorax is a rare but serious complication in children who undergo heart surgery. Its pathogenesis is poorly understood, and invasive surgical treatments are considered only after conservative management fails. Current diagnostic imaging techniques, which could aid decision making for earlier surgical intervention, are difficult to apply. Herein, we deployed near-infrared fluorescence (NIRF) lymphatic imaging to allow the visualization of abnormal lymphatic drainage in an infant with postoperative chylothorax to guide the choice of surgical management. A 5-week-old male infant, who developed chylothoraces after undergoing Norwood surgery for hypoplastic left heart syndrome, was intradermally administered trace doses of indocyanine green in both feet and the left hand. NIRF imaging was then performed at the bedside to visualize lymphatic drainage patterns. Imaging results indicated impeded lymphatic drainage from the feet toward the trunk with no fluorescence in the chest indicating no leakage of peripheral lymph at the thoracic duct. Instead, lymph drainage occurred from the axilla directly into the pleural cavity. As a result of imaging, left pleurodesis was performed to stop the pleural effusion with the result of temporary decrease of left chest tube drainage. Although additional studies are required to understand normal and abnormal lymphatic drainage patterns in infants, we showed the potential of using NIRF lymphatic imaging at the bedside to visualize the lymphatic drainage pathway to guide therapy. Timely management of chylothorax may be improved by using NIRF imaging to understand lymphatic drainage pathways.

Cognitive Decline After Divorce and Widowhood: Is Marital Loss Always a Loss?

Background and Objectives: We used longitudinal data to determine whether the type of marital loss is associated with the rate of cognitive change before and after divorce or widowhood. Previous research found that relationship status was associated with older adults' cognitive performance: married persons performed better on memory assessments and had lower dementia risk than unmarried-cohabitating, never-married, divorced, and widowed persons. However, the end of a marriage may cause distress or reduce distress because a stressor disappears. Questions thus remain about the mechanisms by which marital change affects cognitive outcomes and, specifically, whether termination of marriage can improve cognitive performance for some. Research Design and Methods: Using data from the 1998-2016 waves of the Health and Retirement Study (N = 23,393), we conducted two analyses. First, we used trajectory analysis to create clusters of participants with similar cognitive trajectories and tested the association between participants' cluster membership and marital loss type. Second, we used multilevel modeling to analyze the relationship between participants' cognitive scores while married and following divorce or widowhood and linked these to marital features. Results: Participants who divorced showed no difference in trajectory distribution; widowed participants were more likely to be in the lower-performing and more quickly declining groups. Participants had lower rates of decline following divorce (ß = .136, p < .001), while widowed participants had accelerated decline following spousal death (ß = -0.183, p < .001) and an immediate decline following spousal death (ß = -0.113, p = .028). Discussion and Implications: We found that the type of marital loss was important, and predicted improvements in cognition for some and decrements for others, with individuals who were divorced performing best while those who were widowed or separated but not divorced performing worse.

Quantifying Healthy Aging in Older Veterans Using Computational Audio Analysis.

BACKGROUND: Researchers are increasingly interested in better methods for assessing the pace of aging in older adults, including vocal analysis. The present study sought to determine whether paralinguistic vocal attributes improve estimates of the age and risk of mortality in older adults. METHODS: To measure vocal age, we curated interviews provided by male U.S. World War II Veterans in the Library of Congress collection. We used diarization to identify speakers and measure vocal features and matched recording data to mortality information. Veterans (N = 2 447) were randomly split into testing (n = 1 467) and validation (n = 980) subsets to generate estimations of vocal age and years of life remaining. Results were replicated to examine out-of-sample utility using Korean War Veterans (N = 352). RESULTS: World War II Veterans' average age was 86.08 at the time of recording and 91.28 at the time of death. Overall, 7.4% were prisoners of war, 43.3% were Army Veterans, and 29.3% were drafted. Vocal age estimates (mean absolute error = 3.255) were within 5 years of chronological age, 78.5% of the time. With chronological age held constant, older vocal age estimation was correlated with shorter life expectancy (aHR = 1.10; 95% confidence interval: 1.06-1.15; p < .001), even when adjusting for age at vocal assessment. CONCLUSIONS: Computational analyses reduced estimation error by 71.94% (approximately 8 years) and produced vocal age estimates that were correlated with both age and predicted time until death when age was held constant. Paralinguistic analyses augment other assessments for individuals when oral patient histories are recorded.

Genome-wide identification and spatiotemporal expression analysis of cadherin superfamily members in echinoderms.

BACKGROUND: Cadherins are calcium-dependent transmembrane cell-cell adhesion proteins that are essential for metazoan development. They consist of three subfamilies: classical cadherins, which bind catenin, protocadherins, which contain 6-7 calcium-binding repeat domains, and atypical cadherins. Their functions include forming adherens junctions, establishing planar cell polarity (PCP), and regulating cell shape, proliferation, and migration. Because they are basal deuterostomes, echinoderms provide important insights into bilaterian evolution, but their only well-characterized cadherin is G-cadherin, a classical cadherin that is expressed by many embryonic epithelia. We aimed to better characterize echinoderm cadherins by conducting phylogenetic analyses and examining the spatiotemporal expression patterns of cadherin-encoding genes during Strongylocentrotus purpuratus development. RESULTS: Our phylogenetic analyses conducted on two echinoid, three asteroid, and one crinoid species identified ten echinoderm cadherins, including one deuterostome-specific ortholog, cadherin-23, and an echinoderm-specific atypical cadherin that possibly arose in an echinoid-asteroid ancestor. Catenin-binding domains in dachsous-2 orthologs were found to be a deuterostome-specific innovation that was selectively lost in mouse, while those in Fat4 orthologs appeared to be Ambulacraria-specific and were selectively lost in non-crinoid echinoderms. The identified suite of echinoderm cadherins lacks vertebrate-specific innovations but contains two proteins that are present in protostomes and absent from mouse. The spatiotemporal expression patterns of four embryonically expressed cadherins (fat atypical cadherins 1 and 4, dachsous-2, and protocadherin-9) were dynamic and mirrored the expression pattern of Frizzled 5/8, a non-canonical Wnt PCP pathway receptor protein essential for archenteron morphogenesis. CONCLUSIONS: The echinoderm cadherin toolkit is more similar to that of an ancient bilaterian predating protostomes and deuterostomes than it is to the suite of cadherins found in extant vertebrates. However, it also appears that deuterostomes underwent several cadherin-related innovations. Based on their similar spatiotemporal expression patterns and orthologous relationships to PCP-related and tumor-suppressing proteins, we hypothesize that sea urchin cadherins may play a role in regulating the shape and growth of embryonic epithelia and organs. Future experiments will examine cadherin expression in non-echinoid echinoderms and explore the functions of cadherins during echinoderm development.

Obesity in Late-Life as a Protective Factor Against Dementia and Dementia-Related Mortality.

OBJECTIVE: We estimated the conversion from cognitively normal to mild cognitive impairment (MCI) to probable dementia and death for underweight, normal, overweight, and obese older adults, where the timing of examinations is associated with the severity of dementia. METHODS: We analyzed six waves of the National Health and Aging Trends Study (NHATS). Body mass (BMI) was computed from height and weight. Multi-state survival models (MSMs) examined misclassification probability, time-to-event ratios, and cognitive decline. RESULTS: Participants (n = 6078) were 77 years old, 62% had overweight and/or obese BMI. After adjusting for the effects of cardiometabolic factors, age, sex, and race, obesity was protective against developing dementia (aHR=.44; 95%CI [.29-.67]) and dementia-related mortality (aHR=.63; 95%CI [.42-.95]). DISCUSSION: We found a negative relationship between obesity and dementia and dementia-related mortality, a finding that has been underreported in the literature. The continuing obesity epidemic might complicate the diagnosis and treatment of dementia.

Paper I: Heterogeneous use of registry data for participant identification and primary outcome ascertainment is found in registry-based randomized controlled trials: A scoping review.

OBJECTIVES: Registry-based randomized controlled trials (RRCTs) have potential to address limitations of traditional clinical trials. To describe their current use, information on planned and published RRCTs was identified and synthesized. STUDY DESIGN AND SETTING: A scoping review of published RRCT protocols and reports was conducted. Articles published between 2010 and 2021 identified from electronic database searching, a recent review of RRCTs, and targeted searching for recent RRCT protocols (2018-2021) were screened. Data on trial data sources, types of primary outcomes, and how these primary outcomes were described, selected, and reported were extracted. RESULTS: Ninety RRCT articles (77 reports; 13 protocols) were included. Forty nine (54%) used or planned to rely on registry data for their trial, 26 (29%) used both registry and additional data, and 15 (17%) used the registry solely for recruitment. Primary outcomes were routinely collected from the registry for 66 articles (73%). Only 28 articles (31%) described any methods to promote outcome data quality during or after data collection. Core outcome sets were not used in any of the trials. CONCLUSION: With improvements in registry design, outcome selection, measurement, and reporting, future RRCTs may deliver on promises of efficient, high-quality trials that address clinically relevant questions.

Paper II: thematic framework analysis of registry-based randomized controlled trials provided insights for designing trial ready registries.

OBJECTIVES: Registry-based randomized controlled trials (RRCTs) are increasingly used, promising to address challenges associated with traditional randomized controlled trials. We identified strengths and limitations reported in planned and completed RRCTs to inform future RRCTs. STUDY DESIGN AND SETTING: We conducted an environmental scan of literature discussing conceptual or methodological strengths and limitations of using registries for trial design and conduct (n = 12), followed by an analysis of RRCT protocols (n = 13) and reports (n = 77) identified from a scoping review. Using framework analysis, we developed and refined a conceptual framework of RRCT-specific strengths and limitations. We mapped and interpreted strengths and limitations discussed by authors of RRCT articles using framework codes and quantified the frequencies at which these were mentioned. RESULTS: Our conceptual framework identified six main RRCT strengths and four main RRCT limitations. Considering implications for RRCT conduct and design, we formulated ten recommendations for registry designers, administrators, and trialists planning future RRCTs. CONCLUSION: Consideration and application of empirically underpinned recommendations for future registry design and trial conduct may help trialists utilize registries and RRCTs to their full potential.

Social Determinants of Health Associated With the Development of Sepsis in Adults: A Scoping Review.

Evaluating risk for sepsis is complicated due to limited understanding of how social determinants of health (SDoH) influence the occurence of the disease. This scoping review aims to identify gaps and summarize the existing literature on SDoH and the development of sepsis in adults. DATA SOURCES: A literature search using key terms related to sepsis and SDoH was conducted using Medline and PubMed. STUDY SELECTION: Studies were screened by title and abstract and then full text in duplicate. Articles were eligible for inclusion if they: 1) evaluated at least one SDoH on the development of sepsis, 2) participants were 18 years or older, and 3) the studies were written in English between January 1970 and January 2022. Systematic reviews, meta-analyses, editorials, letters, commentaries, and studies with nonhuman participants were excluded. DATA EXTRACTION: Data were extracted in duplicate using a standardized data extraction form. Studies were grouped into five categories according to the SDoH they evaluated (race, socioeconomic status [SES], old age and frailty, health behaviors, and social support). The study characteristics, key outcomes related to incidence of sepsis, mortality, and summary statements were included in tables. DATA SYNTHESIS: The search identified 637 abstracts, 20 of which were included after full-text screening. Studies evaluating SES, old age, frailty, and gender demonstrated an association between sepsis incidence and the SDoH. Studies that examined race demonstrated conflicting conclusions as to whether Black or White patients were at increased risk of sepsis. Overall, a major limitation of this analysis was the methodological heterogeneity between studies. CONCLUSIONS: There is evidence to suggest that SDoH impacts sepsis incidence, particularly SES, gender, old age, and frailty. Future prospective cohort studies that use standardized methods to collect SDoH data, particularly race-based data, are needed to inform public health efforts to reduce the incidence of sepsis and help clinicians identify the populations most at risk.

Permanent Hydrophobic Surface Treatment Combined with Solvent Vapor-Assisted Thermal Bonding for Mass Production of Cyclic Olefin Copolymer Microfluidic Chips.

A hydrophobic surface modification followed by solvent vapor-assisted thermal bonding was developed for the fabrication of cyclic olefin copolymer (COC) microfluidic chips. The modifier species 1H,1H,2H,2H-perfluorooctyl trichlorosilane (FOTS) was used to achieve the entrapment functionalization on the COC surface, and a hydrophobic surface was developed through the formation of a Si-O-Si crosslink network. The COC surface coated with 40 vol % cyclohexane, 59 vol % acetone, and 1 vol % FOTS by ultrasonic spray 10 and 20 times maintained its hydrophobicity with the water contact angle increasing from ∼86 to ∼115° after storage for 3 weeks. The solvent vapor-assisted thermal bonding was optimized to achieve high bond strength and good channel integrity. The results revealed that the COC chips exposed to 60 vol % cyclohexane and 40 vol % acetone for 120 s have the highest bond strength, with a burst pressure of ∼17 bar, which is sufficient for microfluidics applications such as droplet generation. After bonding, the channel maintained its integrity without any channel collapse. The hydrophobicity was also maintained, proved by the water contact angle of ∼115° on the bonded film, as well as the curved shape of water flow in the chip channel by capillary test. The combined hydrophobic treatment and solvent bonding process show significant benefits for scale-up production compared to conventional hydrophilic treatment for bonding and hydrophobic treatment using surface grafting or chemical vapor deposition since it does not require nasty chemistry, long-term treatment, vacuum chamber, and can be integrated into production line easily. Such a process can also be extended to permanent hydrophilic treatment combined with the bonding process and will lay a foundation for low-cost mass production of plastic microfluidic cartridges.

Functional memory B cells and long-lived plasma cells are generated after a single Plasmodium chabaudi infection in mice.

Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses.

Cor triatriatum sinister with dilated coronary sinus from persistent left superior vena cava: a novel operative approach.

Persistent left superior vena cava is known to be associated with cor triatriatum. The persistent left superior vena cava drains into a dilated coronary sinus and can cause left atrial outflow obstruction by impinging on the posterior wall of the left atrium. Residual obstruction can persist, even after surgical resection of the cor triatriatum membrane. We describe a novel surgical treatment in a patient with cor triatriatum and persistent left superior vena cava.