Photophysiological cycles in Arctic krill are entrained by weak midday twilight during the Polar Night.

Light plays a fundamental role in the ecology of organisms in nearly all habitats on Earth and is central for processes such as vision and the entrainment of the circadian clock. The poles represent extreme light regimes with an annual light cycle including periods of Midnight Sun and Polar Night. The Arctic Ocean extends to the North Pole, and marine light extremes reach their maximum extent in this habitat. During the Polar Night, traditional definitions of day and night and seasonal photoperiod become irrelevant since there are only "twilight" periods defined by the sun's elevation below the horizon at midday; we term this "midday twilight." Here, we characterize light across a latitudinal gradient (76.5° N to 81° N) during Polar Night in January. Our light measurements demonstrate that the classical solar diel light cycle dominant at lower latitudes is modulated during Arctic Polar Night by lunar and auroral components. We therefore question whether this particular ambient light environment is relevant to behavioral and visual processes. We reveal from acoustic field observations that the zooplankton community is undergoing diel vertical migration (DVM) behavior. Furthermore, using electroretinogram (ERG) recording under constant darkness, we show that the main migratory species, Arctic krill (Thysanoessa inermis) show endogenous increases in visual sensitivity during the subjective night. This change in sensitivity is comparable to that under exogenous dim light acclimations, although differences in speed of vision suggest separate mechanisms. We conclude that the extremely weak midday twilight experienced by krill at high latitudes during the darkest parts of the year has physiological and ecological relevance.

Twelve tips for creating and sustaining a peer assessment program of clinical faculty.

While feedback is essential for learning in the health professions, clinical teachers rarely get feedback on their teaching, and the existing feedback is often non-specific and distant from teaching encounters. To enhance clinical teaching, we created a peer assessment program for clinical faculty. This program has been well-received and sustained for five years despite the challenges of faculty turnover and the pandemic. In this article, we identify twelve tips for creating and sustaining a peer assessment program for clinical faculty based on this experience. These tips focus on how to create a culture that supports peer assessment, on how best to implement a peer assessment program in practical terms, and on how to sustain a peer assessment program long-term. We hope these tips help educators receive better feedback about their clinical teaching and improve the future care delivered by our learners.

Does the implementation of a trauma system affect injury-related morbidity and economic outcomes? A systematic review.

BACKGROUND: Trauma accounts for a huge burden of disease worldwide. Trauma systems have been implemented in multiple countries across the globe, aiming to link and optimise multiple aspects of the trauma care pathway, and while they have been shown to reduce overall mortality, much less is known about their cost-effectiveness and impact on morbidity. METHODS: We performed a systematic review to explore the impact the implementation of a trauma system has on morbidity, quality of life and economic outcomes, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All comparator study types published since 2000 were included, both retrospective and prospective in nature, and no limits were placed on language. Data were reported as a narrative review. RESULTS: Seven articles were identified that met the inclusion criteria, all of which reported a pre-trauma and post-trauma system implementation comparison in high-income settings. The overall study quality was poor, with all studies demonstrating a severe risk of bias. Five studies reported across multiple types of trauma patients, the majority describing a positive impact across a variety of morbidity and health economic outcomes following trauma system implementation. Two studies focused specifically on traumatic brain injury and did not demonstrate any impact on morbidity outcomes. DISCUSSION: There is currently limited and poor quality evidence that assesses the impact that trauma systems have on morbidity, quality of life and economic outcomes. While trauma systems have a fundamental role to play in high-quality trauma care, morbidity and disability data can have large economic and cultural consequences, even if mortality rates have improved. The sociocultural and political context of the surrounding healthcare infrastructure must be better understood before implementing any trauma system, particularly in resource-poor and fragile settings. PROSPERO REGISTRATION NUMBER: CRD42022348529 LEVEL OF EVIDENCE: Level III.

Understanding the impact of children's and young people's self-harm on parental well-being: a systematic literature review of qualitative and quantitative findings.

BACKGROUND: Self-harm in children and young people is increasing. Parents are vital in supporting young people; however, parents may experience distress linked to the self-harm. Previous reviews have highlighted the emotional impact and need for information and support, however, have not elucidated the relationships between these themes, nor examined the quantitative data examining parents' well-being. METHODS: We conducted a mixed methods review, with qualitative meta-synthesis focusing on links between themes and quantitative synthesis of parental well-being findings, including pooled means. PsycInfo, Medline, EMBASE, AMED, CINHAL and Web of Science were searched to identify relevant records. References of included studies were also searched. Every abstract was screened by two authors. Data were extracted by one author and checked by another. RESULTS: We identified 39 reports of 32 studies: 16 with qualitative data and 17 with quantitative data (one had both). Qualitative findings showed how parents' emotions were associated to their knowledge and beliefs about self-harm. Parents' emotions often evidenced the need to self-care, but emotions of guilt reduced engagement in self-care. How parents supported their young person was linked to their knowledge, and the management of their own emotions, and influenced if they could engage in self-care. Quantitative findings were mixed, however suggested poor general mental health amongst these parents. CONCLUSIONS: Further good quality quantitative studies are needed, with measurement of psychological mechanisms that may underpin parental distress. Current evidence supports peer-support and interventions that go beyond information provision to address the connected factors of knowledge, emotion, self-care, and parenting behaviours.

The vulnerability to COVID-19 of migrants in large urban areas: structural exacerbators and community-level mitigators.

BACKGROUND: Despite research on large urban areas in the context of COVID-19, evidence on how these settings impact migrants is still limited. OBJECTIVE: To explore exacerbating and mitigating factors of large urban areas on migrants' vulnerabilities during the COVID-19 pandemic. METHODS: We conducted a systematic review of peer-reviewed studies published between 2020 and 2022, focused on migrants (foreign-born individuals who have not been naturalized in the host country, regardless of legal immigration status) in urban areas with a population >500 000. After screening 880 studies, 29 studies were included and categorized within the following thematic framework: (i) pre-existing inequities, (ii) governance strategies, (iii) urban design and (iv) engagement of civil society organizations (CSOs). RESULTS: Exacerbating factors include pre-existing inequities (e.g. unemployment, financial instability and barriers to healthcare access), exclusionary government responses (e.g. ineligibility for relief funds or unemployment benefits) and residential segregation. Mitigating community-level factors include the engagement of CSOs to fill institutional and governmental gaps through service provision and use of technology. CONCLUSIONS: We recommend increased attention to pre-existing structural inequities faced by migrants, more inclusive governance strategies and partnerships between government and CSOs to improve the design and delivery of services to migrants in large urban areas. More research is needed on how urban design can be utilized to mitigate COVID-19 impacts on migrant communities. The factors identified in this systematic review should be considered as part of migrant-inclusive emergency preparedness strategies to address the disproportionate impact of health crises on migrant communities.

A marine zooplankton community vertically structured by light across diel to interannual timescales.

The predation risk of many aquatic taxa is dominated by visually searching predators, commonly a function of ambient light. Several studies propose that changes in visual predation will become a major climate-change impact on polar marine ecosystems. The High Arctic experiences extreme seasonality in the light environment, from 24 h light to 24 h darkness, and therefore provides a natural laboratory for studying light and predation risk over diel to seasonal timescales. Here, we show that zooplankton (observed using acoustics) in an Arctic fjord position themselves vertically in relation to light. A single isolume (depth-varying line of constant light intensity, the value of which is set at the lower limit of photobehaviour reponses of Calanus spp. and krill) forms a ceiling on zooplankton distribution. The vertical distribution is structured by light across timescales, from the deepening of zooplankton populations at midday as the sun rises in spring, to the depth to which zooplankton ascend to feed during diel vertical migration. These results suggest that zooplankton might already follow a foraging strategy that will keep visual predation risk roughly constant under changing light conditions, such as those caused by the reduction of sea ice, but likely with energetic costs such as lost feeding opportunities as a result of altered habitat use.

Outcomes for carotid endarterectomy in nonagenarians.

OBJECTIVE: Carotid endarterectomy (CEA) is a well-established procedure with prospective randomized data demonstrating the benefit of stroke prevention. With the aging of the population, there are limited data published for nonagenarians, especially for asymptomatic stenosis. This study investigated 30-day morbidity and mortality as well as late survival in symptomatic and asymptomatic nonagenarians with severe carotid stenosis undergoing CEA. METHODS: A retrospective review was conducted of a single vascular surgery group's registry involving multiple hospitals between November 1994 and June 2017 for all primary CEAs of patients ≥90 years old at the time of surgery. The exclusion criterion was redo surgery or bilateral CEAs. Demographic data, sex, symptoms, risk factors, and postoperative complications were analyzed. Survival analysis was conducted using SPSS software (IBM Corp, Armonk, NY) for the specific end point 30-day morbidity or mortality and late survival. RESULTS: There were 77 patients (44 male [57%]) who underwent CEA for symptomatic (44 [57%]) and asymptomatic (33 [43%]) internal carotid artery stenosis with a median age of 92 years; 23 women were symptomatic compared with 21 men, and 23 men were asymptomatic compared with 10 women. Symptomatic patients included amaurosis fugax (n = 3), stroke (n = 16), and transient ischemic attack (n = 25). CEAs were performed using the eversion technique under cervical block with selective shunting. The 30-day morbidity included one (2.3%) nonfatal myocardial infarction and one (2.3%) ischemic stroke in the symptomatic group compared with one (3%) patient having a nonfatal myocardial infarction and none with ischemic stroke in the asymptomatic group. One patient of the symptomatic group required return to the operating room for hematoma evacuation. The 30-day mortality was 2.3% in the symptomatic group compared with 6.1% in the asymptomatic group. There was no statistical difference in survival based on sex (P = .444). The symptomatic and asymptomatic groups had similar median survival of 27.7 months and 29.4 months (P = .987), respectively. CONCLUSIONS: The aging population adds increasing difficulty in decision-making for surgical intervention on carotid stenosis. CEA in nonagenarians is associated with reasonably low 30-day rates of ischemic stroke and myocardial infarction in our small study. However, enthusiasm for asymptomatic CEA in this population must be tempered by low survival rates.

Nitrate supply and uptake in the Atlantic Arctic sea ice zone: seasonal cycle, mechanisms and drivers.

Nutrient supply to the surface ocean is a key factor regulating primary production in the Arctic Ocean under current conditions and with ongoing warming and sea ice losses. Here we present seasonal nitrate concentration and hydrographic data from two oceanographic moorings on the northern Barents shelf between autumn 2017 and summer 2018. The eastern mooring was sea ice-covered to varying degrees during autumn, winter and spring, and was characterized by more Arctic-like oceanographic conditions, while the western mooring was ice-free year-round and showed a greater influence of Atlantic water masses. The seasonal cycle in nitrate dynamics was similar under ice-influenced and ice-free conditions, with biological nitrate uptake beginning near-synchronously in early May, but important differences between the moorings were observed. Nitrate supply to the surface ocean preceding and during the period of rapid drawdown was greater at the ice-free more Atlantic-like western mooring, and nitrate drawdown occurred more slowly over a longer period of time. This suggests that with ongoing sea ice losses and Atlantification, the expected shift from more Arctic-like ice-influenced conditions to more Atlantic-like ice-free conditions is likely to increase nutrient availability and the duration of seasonal drawdown in this Arctic shelf region. The extent to which this increased nutrient availability and longer drawdown periods will lead to increases in total nitrate uptake, and support the projected increases in primary production, will depend on changes in upper ocean stratification and their effect on light availability to phytoplankton as changes in climate and the physical environment proceed. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'.

Impact of a Perioperative Prophylaxis Guideline on Post-Cardiothoracic Surgery Atrial Fibrillation.

BACKGROUND: National practice guidelines do not provide clear recommendations on combination pharmacological regimens to reduce cardiothoracic surgery (CTS) postoperative atrial fibrillation (POAF). OBJECTIVE: This study examines if there is a reduction in POAF rates after implementing a perioperative prophylaxis guideline that includes amiodarone, ß-blockers, and high-intensity statins. METHODS: Data were retrospectively collected on 400 adults (200 patients pre-guideline implementation and 200 patients post-guideline implementation) with a CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age, Diabetes Mellitus, and Vascular Disease) score of at least 3 points after CTS. Data were collected on the incidence of POAF lasting more than 5 minutes and secondary outcomes, including the length of hospitalization, guideline adherence rate, adverse events, and timeliness of POAF treatment. RESULTS: Guideline implementation increased prophylactic amiodarone ( P < 0.0001), statin ( P = 0.029), and high-intensity statin ( P = 0.002) use without changing ß-blocker use (64.5% vs 67.0%, P = 0.673) and reduced POAF (39.5% vs 52.0%, P = 0.016) and ventricular tachycardia (15.5% vs 24.5%, P = 0.034) compared with preguideline rates. Length of hospitalization and other postoperative adverse events, including stroke and mortality, were not statistically different. Subgroup analyses of patients who were adherent to both the amiodarone and ß-blocker recommendations (28% of the total) or to all 3 recommended therapies (24% of the total) had significant decreases in POAF ( P = 0.001; P < 0.001), length of hospitalization ( P = 0.023; P = 0.049), length of intensive care unit stay ( P = 0.045; P = 0.040), and ventricular tachycardia ( P = 0.008; P = 0.017) compared with preguideline patients, respectively. CONCLUSIONS: A perioperative guideline of amiodarone, ß-blockers, and high-intensity statins reduced POAF, but better benefits may result from enhanced adherence.

Qualitatively Assessing the Experiences of College Students Completing AlcoholEdu: Do Participants Report Altering Behavior After Intervention?

To reduce college student drinking and associated alcohol-related consequences, many universities are turning to e-interventions, such as AlcoholEdu. To date, however, results of evaluations examining the impact of AlcoholEdu are mixed. Among these evaluations, few qualitative assessments have examined the experiences and perceptions of students who complete AlcoholEdu. This investigation aimed to assess whether students (a) find the program educational and engaging, (b) implemented specific strategies learned from participation, and (c) self-report altering their behavior as a result of participation. Even though respondents universally reported an increase in alcohol-related knowledge, there was an evident disconnect between this knowledge and their actual behavior. In other words, respondents reported that they did not implement what was taught in AlcoholEdu. Moreover, students highlighted several limitations associated with the program that would have influenced its overall impact, such as ignoring video segments of the program and clicking through assessments simply to complete the task. If used, college administrators and health professionals should implement e-interventions such as AlcoholEdu as one component of a multifaceted approach rather than a panacea for the current high-risk drinking practices of college students.

Public involvement and public engagement: An example of convergent evolution? Findings from a conceptual qualitative review of patient and public involvement, and public engagement, in health and scientific research.

Objective: Patient and public involvement (PPI) in health research is now well-established, whilst science, technology, engineering and mathematics (STEM) research has shifted from a focus on science communication alone to public engagement (PE) within its research processes. Despite frequently drawing on similar theoretical influences, and practical motivations, there is often a lack of dialogue between such settings meaning shared learning, practice and evidence from these two sectors are rarely pooled. Methods: In this article, we examine findings from a conceptual review of literature gathered between 1996 and 2019. Results: Analyzing 142 peer-reviewed articles, we ascertain shared definitions and concepts in patient and public involvement and public engagement, identifying key differences and similarities. Conclusion: The literature we review supports the notion that, in terms of origins, there are two distinct traditions, one based in science communication and one based in what we describe as public involvement in shared decision-making. Innovation: We find evidence that the two traditions are converging but our work also calls for the need for further conversations between these two settings, which are exploring intersecting issues but from parallel pathways.

In Vitro Proliferation of MG-63 Cells in Additively Manufactured Ti-6Al-4V Biomimetic Lattice Structures with Varying Strut Geometry and Porosity.

Lattice structures have demonstrated the ability to provide secondary stability in orthopedic implants by promoting internal bone growth. In response to the growing prevalence of lattices in orthopedic design, we investigated the effects of porosity and unit cell geometry in additively manufactured Ti-6Al-4V biomimetic lattice structures on the osteogenesis of human MG-63 osteoblastic cell lines in vitro. We analyzed glucose consumption, alkaline phosphatase (ALP) concentration, and end-of-culture cell count as markers for osteogenic growth. Two different strut geometries were utilized (cubic and body-centered cubic), along with four different pore sizes (400, 500, 600, and 900 µm, representing 40-90% porosity in a 10 mm cube), in addition to a solid specimen. Structural characterization was performed using scanning electron microscopy. The results indicated that lattices with a 900 µm pore size exhibited the highest glucose consumption, the greatest change in ALP activity, and the highest cell count when compared to other pore sizes. Cubic 900 µm lattice structures outperformed other specimens in facilitating the maturation of viable MG-63 cells from the formation to the mineralization phase of bone remodeling, offering the most promise for osseointegration in additively manufactured titanium implants in the future. However, irrespective of a particular pore size or unit cell geometry, it was found that all the lattices were capable of promoting osteogenic growth due to surface roughness in the printed parts.

Lessons learnt from the implementation of the Covid-19 vaccination programme in the Southwest of England.

BACKGROUND: Vaccination remains one of the most successful public health interventions in preventing severe disease and death. The roll-out of Covid-19 vaccination programmes has helped protect billions of people around the world against Covid-19. Most of these programmes have been unprecedented in terms of scale and resources, and have been implemented at times of significant humanitarian crisis. This study aims to outline the lessons learnt from the implementation of a regional Covid-19 vaccination programme. These will help inform emergency preparedness and future crisis management. METHODS: This qualitative study sought to explore the key drivers to the successful implementation of the Covid-19 vaccination programme in a region in the Southwest of England, applying the Normalisation Process Theory lens (NPT) to examine multi-stakeholder perspectives. Data collection involved semi-structured interviews with 75 participants. Document analysis was also used to corroborate the findings emerging from the interviews. Inductive thematic analysis of the data was used to identify the key drivers for the successful implementation of the programme. The NPT lens was then applied to map the themes identified to the domains and constructs of the framework. RESULTS: Ten key drivers to the successful implementation of the Covid-19 vaccination programme locally were identified, including: the clarity and consistency of the programme's goal; the diverse representation of stakeholders within the programme leadership team and the mechanisms created by this team to ensure psychological safety, autonomy, operational flexibility and staff empowerment; Communication and data specialists' input, and collaboration with local communities to maximise the reach of the programme; and allocating funding to tackle health inequalities. CONCLUSIONS: This study highlights the lessons learnt from the implementation of the Covid-19 vaccination programme at a local level, and the mechanisms that can be used in future crises to respond efficiently to the needs of individuals, communities and governments.

Evaluating patient factors, operative management and postoperative outcomes in trauma laparotomy patients worldwide: a protocol for a global observational multicentre trauma study.

INTRODUCTION: Trauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed operation. Variation likely exists in how these patients are managed and their subsequent outcomes, yet very little global data on the topic currently exists. The objective of the GOAL-Trauma study is to evaluate both patient and injury factors for those undergoing trauma laparotomy, their clinical management and postoperative outcomes. METHODS: We describe a planned prospective multicentre observational cohort study of patients undergoing trauma laparotomy. We will include patients of all ages who present to hospital with a blunt or penetrating injury and undergo a trauma laparotomy within 5 days of presentation to the treating centre. The study will collect system, patient, process and outcome data, following patients up until 30 days postoperatively (or until discharge or death, whichever is first). Our sample size calculation suggests we will need to recruit 552 patients from approximately 150 recruiting centres. DISCUSSION: The GOAL-Trauma study will provide a global snapshot of the current management and outcomes for patients undergoing a trauma laparotomy. It will also provide insight into the variation seen in the time delays for receiving care, the disease and patient factors present, and patient outcomes. For current standards of trauma care to be improved worldwide, a greater understanding of the current state of trauma laparotomy care is paramount if appropriate interventions and targets are to be identified and implemented.

The Impact of Trauma System Implementation on Patient Quality of Life and Economic Burden: A Systematic Review Study Protocol.

Background: Trauma accounts for 10% of global mortality, with increasing rates disproportionally affecting low- and middle-income countries. In an attempt to improve clinical outcomes after injury, trauma systems have been implemented in multiple countries over recent years. However, whilst many studies have subsequently demonstrated improvements in overall mortality outcomes, less is known about the impact trauma systems have on morbidity, quality of life, and economic burden. This systematic review seeks to assess the existing evidence base for trauma systems with these outcome measures. Methods: This review will include any study that assesses the impact implementation of a trauma system has on patient morbidity, quality of life, or economic burden. Any comparator study, including cohort, case-control, and randomised controlled studies, will be included, both retrospective or prospective in nature. Studies conducted from any region in the world and involving any age of patient will be included. We will collect data on any morbidity outcomes, health-related quality of life measures, or health economic assessments reported. We predict a high heterogeneity in these outcomes used and will therefore keep inclusion criteria broad. Discussion: Previous reviews have shown the significant improvements that can be achieved in mortality outcomes with the implementation of an organised trauma system, however the wider impact they can have on morbidity outcomes, quality of life measures, and the economic burden of trauma, is less well described. This systematic review will present all available data on these outcomes, helping to better characterise both the societal and economic impact of trauma system implementation. Highlights: Trauma systems are known to improve mortality rates, however less in known on the impact they have on morbidity outcomes, quality of life, and economic burdenWe aim to perform a systematic review to identify any comparator study that assesses the impact implementation of a trauma system on these outcomesUnderstanding the impact trauma systems can have on wider parameters, such as economic and quality of life outcomes, is crucial to allow governments globally to appropriately allocate often limited healthcare resources.PROSPERO registration number: CRD42022348529.

Animal behavior is central in shaping the realized diel light niche.

Animal behavior in space and time is structured by the perceived day/night cycle. However, this is modified by the animals' own movement within its habitat, creating a realized diel light niche (RDLN). To understand the RDLN, we investigated the light as experienced by zooplankton undergoing synchronized diel vertical migration (DVM) in an Arctic fjord around the spring equinox. We reveal a highly dampened light cycle with diel changes being about two orders of magnitude smaller compared to the surface or a static depth. The RDLN is further characterized by unique wavelength-specific irradiance cycles. We discuss the relevance of RDLNs for animal adaptations and interactions, as well as implications for circadian clock entrainment in the wild and laboratory.

Leaving No One Behind: Interventions and Outcomes of the COVID-19 Vaccine Maximising Uptake Programme.

The devastating impact of COVID-19 on individuals and communities has accelerated the development of vaccines and the deployment of ambitious vaccination programmes to reduce the risks of infection, infection transmission and symptom severity. However, many people delay or refuse to get vaccinated against COVID-19, for many complex reasons. Vaccination programmes that are tailored to address individual and communities' COVID-19 concerns can improve vaccine uptake rates and help achieve the required herd-immunity threshold. The Maximising Uptake Programme has led to the vaccination of 7979 people from February-August 2021 in the South West of England, UK, who are at high risk of severe illness from COVID-19 and/or may not access the COVID-19 vaccines through mass vaccination centres and general practices. These include: people experiencing homelessness; non-English-speaking people; people from minority ethnic groups; refugees and asylum seekers; Gypsy, Roma, Travelers and boat people; and those who are less able to access vaccination centres, such as people with learning difficulties, serious mental illness, drug and alcohol dependence, people with physical and sensory impairment, and people with dementia. Outreach work coupled with a targeted communication and engagement campaign, co-designed with community leaders and influencers, have led to significant engagement and COVID-19 vaccine uptake among the target populations.

Shine a light: Under-ice light and its ecological implications in a changing Arctic Ocean.

The Arctic marine ecosystem is shaped by the seasonality of the solar cycle, spanning from 24-h light at the sea surface in summer to 24-h darkness in winter. The amount of light available for under-ice ecosystems is the result of different physical and biological processes that affect its path through atmosphere, snow, sea ice and water. In this article, we review the present state of knowledge of the abiotic (clouds, sea ice, snow, suspended matter) and biotic (sea ice algae and phytoplankton) controls on the underwater light field. We focus on how the available light affects the seasonal cycle of primary production (sympagic and pelagic) and discuss the sensitivity of ecosystems to changes in the light field based on model simulations. Lastly, we discuss predicted future changes in under-ice light as a consequence of climate change and their potential ecological implications, with the aim of providing a guide for future research.

Venous Thromboembolism Prophylaxis in Underweight Hospitalized Patients.

There is limited evidence about optimal anticoagulant dosing for venous thromboembolism (VTE) prophylaxis in underweight patients. The purpose of this study was to characterize dosing strategies used in underweight patients and compare the incidence of bleeding and VTE to patients receiving a standard dose. This multi-center retrospective study evaluated medicine patients who weighed 45 kilograms or less and received VTE prophylaxis with unfractionated heparin or enoxaparin. We categorized subjects into groups as either standard or reduced dose and compared the incidence of bleeding and VTE between groups. Of the 300 patients included in the outcome analysis, 40.7% received a reduced dose regimen, most often enoxaparin 30 mg daily. Standard dose was associated with major bleeding compared with reduced dose, when adjusted for age, gender and admission hemoglobin (odds ratio 4.73, 95% confidence interval 1.05 to 21.34). Incidence of clinically relevant non-major bleeding (2.4% vs. 1.1%) and VTE (0.6% vs. 0%) were similar between groups. Anticoagulant dose reduction for VTE prophylaxis in underweight hospitalized medicine patients is common practice and associated with less major bleeding.

The Opposing Role of Propionate in Modulating Listeria monocytogenes Intracellular Infections.

Listeria monocytogenes is a Gram-positive, intracellular pathogen responsible for the highly fatal foodborne illness listeriosis. Establishing intracellular infections requires the coordinated expressions of a variety of virulence factors, such as the pore-forming toxin listeriolysin O (LLO), in response to various intra- and extracellular signals. For example, we previously reported that L. monocytogenes differentially modulated LLO production in response to exogenous propionate, a short chain fatty acid either used in salt form as a human food ingredient or produced endogenously by gut microbial fermentation. Therefore, propionate is likely a continuously present signal throughout the L. monocytogenes transmission and infection process. However, little is known about the role of propionate in modulating L. monocytogenes-host interactions. Here we investigated the impact of propionate treatment on L. monocytogenes intracellular infections using cell culture infection models. Propionate treatment was performed separately on L. monocytogenes or host cells before or during infections to better distinguish pathogen-versus-host responses to propionate. Intracellular CFU in RAW264.7 macrophages and plaque diameters in L-fibroblasts were measured as proxy for intracellular infection outcomes. Nitrite levels and cellular morphology were also measured to assess host responses to propionate. We found that propionate pretreatment of anaerobic, but not aerobic, L. monocytogenes significantly enhanced subsequent intracellular infections in both cell types and nitrite production by infected macrophages. Propionate treatment of uninfected macrophages significantly altered cell morphology, seen by longer cells and greater migration, and reduced nitrite concentration in activated macrophages. Treatment of macrophages with propionate prior to or during infections significantly inhibited intracellular growth of L. monocytogenes, including those pre-treated with propionate. These results showcased an opposing effect of propionate on L. monocytogenes intracellular infections and strongly support propionate as an important signaling molecule for both the pathogen and the host cell that can potentially alter the outcome of L. monocytogenes-host interactions.