When Direct Oral Anticoagulants Should Not Be Standard Treatment: JACC State-of-the-Art Review.

For most patients, direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for stroke prevention in atrial fibrillation and for venous thromboembolism treatment. However, randomized controlled trials suggest that DOACs may not be as efficacious or as safe as the current standard of care in conditions such as mechanical heart valves, thrombotic antiphospholipid syndrome, and atrial fibrillation associated with rheumatic heart disease. DOACs do not provide a net benefit in conditions such as embolic stroke of undetermined source. Their efficacy is uncertain for conditions such as left ventricular thrombus, catheter-associated deep vein thrombosis, cerebral venous sinus thrombosis, and for patients with atrial fibrillation or venous thrombosis who have end-stage renal disease. This paper provides an evidence-based review of randomized controlled trials on DOACs, detailing when they have demonstrated efficacy and safety, when DOACs should not be the standard of care, where their safety and efficacy are uncertain, and areas requiring further research.

Changes in Gastric Pathology after H. pylori Treatment in Community-Driven Research Aimed at Gastric Cancer Prevention.

Community-driven projects have characterized Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns about the frequent diagnosis of Hp infection among community members and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Projects included breath-test screening for Hp infection, gastroscopy with gastric biopsies, and treatment to eliminate Hp infection. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This analysis describes changes in precancerous gastric pathologies in project participants who had gastroscopy before baseline treatment during 2008-2013 and again in 2017. Throughout the study period, the same pathologist graded Hp density, active gastritis, chronic gastritis, atrophic gastritis, and intestinal metaplasia using the updated Sydney System. Of 310 participants from three communities with baseline pathology data, 69 had follow-up pathology data. Relative to baseline, the prevalence of Hp infection and precancerous gastric pathology was substantially lower at follow-up; most participants who were Hp-positive at baseline and Hp-negative at follow-up had reduced severity of active, chronic, and/or atrophic gastritis at follow-up. Though follow-up numbers are small, these results yield evidence that successful Hp treatment has the potential to reduce the risk of gastric cancer in Arctic Indigenous communities.

Major cardiovascular events after COVID-19, event rates post-vaccination, antiviral or anti-inflammatory therapy, and temporal trends: Rationale and methodology of the CORONA-VTE-Network study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and thrombotic events in the early post-infection period and during convalescence. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied. METHODS: Adult patients, aged ≥18 years, with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at the participating centers of the registry are eligible for inclusion. A total of 10,000 patients have been included in this multicenter study, with Brigham and Women's Hospital (Boston, MA) serving as the coordinating center. Other sites include Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System. Data elements will be ascertained manually for accuracy. The two main outcomes are 1) a composite of venous or arterial thrombotic events, and 2) a composite of major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Clinical outcomes are adjudicated by independent physicians. Vaccination status and time of inclusion in the study will be ascertained for subgroup-specific analyses. Outcomes are pre-specified to be reported separately for hospitalized patients versus those who were initially receiving outpatient care. Outcomes will be reported at 30-day and 90-day follow-up. Data cleaning at the sites and the data coordinating center and outcomes adjudication process are in-progress. CONCLUSIONS: The CORONA-VTE-Network study will share contemporary information related to rates of cardiovascular and thrombotic events in patients with COVID-19 overall, as well as within key subgroups, including by time of inclusion, vaccination status, patients undergoing hemodialysis, the elderly, and sex-informed analyses such as comparison of women and men, or among pregnant and breastfeeding women.

Effects of solar radiations on stratum corneum hydration: Part I, protective role of skin surface lipids.

This study used Raman spectroscopy to develop a new approach to evaluate the effects of solar radiation on the stratum corneum (SC). The method measures the SC's hydration and dehydration kinetics by calculating the vOH/vCH ratio to monitor the relative water content during the drying process. The study also investigated the role of skin surface lipids (SSLs) in protecting the SC from solar radiation. The SSLs film is a complex mixture of free fatty acids, triglycerides, wax esters, squalene, free and esterified cholesterols, that play a crucial role in the skin's barrier function. The results showed that solar radiation alters the water content and balance within the SC, and SSLs provide protection by acting as an optical filter by absorbing some of the energy of the solar light. This is confirmed by high temperature gas chromatography coupled to mass spectrometry analyses by revealing a decrease in specific lipids after irradiating the SSLs .

In vitro Raman imaging of human macrophages: Impact of eicosapentaenoic acid on the hydrolysis of cholesterol esters in lipid droplets.

Atherosclerosis - a cardiovascular disease and the primary cause of morbidity and mortality in industrialized countries - is linked to the existence of atherosclerotic plaques characterized by cholesterol-laden macrophages called foam cells. In these cells, cholesterol esters associated with triglycerides form lipid droplets (LD). The only way to remove this excess cholesterol is to promote free cholesterol efflux from macrophages to specific acceptors. It has been shown recently that eicosapentaenoic acid (EPA) reduces efflux on cholesterol-loaded THP-1 macrophages in vitro due to decreased cholesterol esters hydrolysis. These in vitro observations could reflect EPA's difficulty in facilitating in vivo the antiatherogenic process of cholesterol efflux within advanced atherosclerotic plaques. This work aims to study in vitro the impact of EPA on cholesterol esters hydrolysis in the LD of human THP-1 macrophages using vibrational Raman microspectroscopy. For this, we used deuterated EPA and recorded spectral images at the cell scale after different hydrolysis times. RESULTS: showed that EPA is involved in forming triglycerides and phospholipids of LD. Hydrolysis kinetics slowed down after 24 h, triglycerides increased, and the intensity of the characteristic bands linked to deuteration decreased. The size of LD without hydrolysis (H0) is higher than that after 24 h (H1) or 48 h (H2) of hydrolysis. The size decrease is sharper when going from H0 to H1 than from H1 to H2. Principal component analysis illustrated data' projection according to the cellular compartment, the hydrolysis time, and the supplementation of the medium.

Text Message Reminders to Improve Immunization Appointment Attendance in Alberta, Canada: The Childhood Immunization Reminder Project Pilot Study.

BACKGROUND: Vaccine coverage for 18-month-old children in Canada is often below the recommended level, which may be partially because of parental forgetfulness. SMS text message reminders have been shown to potentially improve childhood immunization uptake but have not been widely used in Alberta, Canada. In addition, it has been noted that language barriers may impede immunization service delivery but continue to remain unaddressed in many existing reminder and recall systems. OBJECTIVE: This study aimed to assess the effectiveness and acceptability of using SMS text messages containing a link to web-based immunization information in different languages to remind parents of their child's 18-month immunization appointment. METHODS: The Childhood Immunization Reminder Project was a pilot intervention at 2 public health centers, one each in Lethbridge and Edmonton, Alberta, Canada. Two SMS text message reminders were sent to parents: a booking reminder 3 months before their child turned 18 months old and an appointment reminder 3 days before their scheduled appointment. Booking reminders included a link to the study website hosting immunization information in 9 languages. To evaluate intervention effectiveness, we compared the absolute attendance no-show rates before the intervention and after the intervention. The acceptability of the intervention was evaluated through web-based surveys completed by parents and public health center staff. Google Analytics was used to determine how often web-based immunization information was accessed, from where, and in which languages. RESULTS: Following the intervention, the health center in Edmonton had a reduction of 6.4% (95% CI 3%-9.8%) in appointment no-shows, with no change at the Lethbridge Health Center (0.8%, 95% CI -1.4% to 3%). The acceptability surveys were completed by 222 parents (response rate: 23.9%) and 22 staff members. Almost all (>95%) respondents indicated that the reminders were helpful and provided useful suggestions for improvement. All surveyed parents (222/222, 100%) found it helpful to read web-based immunization information in their language of choice. Google Analytics data showed that immunization information was most often read in English (118/207, 57%), Punjabi (52/207, 25.1%), Arabic (13/207, 6.3%), Spanish (12/207, 5.8%), Italian (4/207, 1.9%), Chinese (4/207, 1.9%), French (2/207, 0.9%), Tagalog (1/207, 0.5%), and Vietnamese (1/207, 0.5%). CONCLUSIONS: The study's findings support the use of SMS text message reminders as a convenient and acceptable method to minimize parental forgetfulness and potentially reduce appointment no-shows. The diverse languages accessed in web-based immunization information suggest the need to provide appropriate translated immunization information. Further research is needed to evaluate the impact of SMS text message reminders on childhood immunization coverage in different settings.

Studying the effects of suberythemal UV doses on the human stratum corneum by in vivo confocal Raman spectroscopy

Background: The stratum corneum (SC) plays an important role in skin barrier function. It acts as a protective barrier against water loss, eliminates foreign substances and micro-organisms and acts against harmful effects of UVR. Objectives: Our aim was to study the impact of suberythemal doses of UVA and UVB exposure on the molecular structure, organization and barrier function of the SC by following different Raman descriptors. Materials & Methods: Twenty female volunteers, aged 20-30 years, with healthy skin were enrolled. Doses of 95 mJ/cm² UVA and 15 mJ/cm² UVB were applied to volunteers' forearms. In vivo Raman measurements were performed at irradiated and control regions. Results: The impact of UVA and UVB irradiation was observed following several Raman descriptors, i.e. the ratio of vasymCH2/vsymCH2 (2885 cm-1/2850 cm-1) corresponding to the organizational order of the lipid bilayer. Water content and mobility descriptors were obtained by calculating vOH/vCH ratio. Finally, protein secondary structure was evaluated based on the 1670 cm-1/1650 cm-1 ratio related to ß sheets and α helices, respectively. Conclusion: UVA induced a loosening of the lateral packing of lipids immediately after irradiation. In contrast, delayed impact caused a tightening of the lipid barrier, an increase in water content -mainly in the unbound water fraction and a higher relative amount of ß sheets in SC proteins. Overall, these observations may explain the thickening of the SC observed in previous studies. A UVB dose of 15 mJ/cm² was apparently below the threshold necessary to induce significant changes despite the trends observed in this study.

Transition to endemic: acceptance of additional COVID-19 vaccine doses among Canadian adults in a national cross-sectional survey.

BACKGROUND: Additional doses of COVID-19 vaccine have been proposed as solutions to waning immunity and decreased effectiveness of primary doses against infection with new SARS-CoV-2 variants. However, the effectiveness of additional vaccine doses relies on widespread population acceptance. We aimed to assess the acceptance of additional COVID-19 vaccine doses (third and annual doses) among Canadian adults and determine associated factors. METHODS: We conducted a national, cross-sectional online survey among Canadian adults from October 14 to November 12, 2021. Weighted multinomial logistic regression analyses were used to identify sociodemographic and health-related factors associated with third and annual dose acceptance and indecision, compared to refusal. We also assessed influences on vaccine decision-making, and preferences for future vaccine delivery. RESULTS: Of 6010 respondents, 70% reported they would accept a third dose, while 15.2% were undecided. For annual doses, 64% reported acceptance, while 17.5% were undecided. Factors associated with third dose acceptance and indecision were similar to those associated with annual dose acceptance and indecision. Previous COVID-19 vaccine receipt, no history of COVID-19 disease, intention to receive an influenza vaccine, and increasing age were strongly associated with both acceptance and indecision. Chronic illness was associated with higher odds of acceptance, while self-reported disability was associated with higher odds of being undecided. Higher education attainment and higher income were associated with higher odds of accepting additional doses. Minority first language was associated with being undecided about additional doses, while visible minority identity was associated with being undecided about a third dose and refusing an annual dose. All respondents reported government recommendations were an important influence on their decision-making and identified pharmacy-based delivery and drop-in appointments as desirable. Co-administration of COVID-19 and influenza vaccines was viewed positively by 75.5% of the dose 3 acceptance group, 12.3% of the undecided group, and 8.4% of the refusal group. CONCLUSIONS: To increase acceptance, targeted interventions among visible minority and minority language populations, and those with a disability, are required. Offering vaccination at pharmacies and through drop-in appointments are important to facilitate uptake, while offering COVID-19/influenza vaccine co-administration may have little benefit among those undecided about additional doses.

Using Health Economics to Inform Immunization Policy Across All Levels of Government.

Publicly funded immunization programs have grown in both complexity and scope, resulting in increased costs and more complex programmatic decision making. Economic evaluations can provide crucial information to support informed decision making. While very few countries have National Immunization Technical Advisory Groups that analyze economic information, many have started to develop processes for this purpose. Since these guidelines are being developed at the national level, we propose that regional jurisdictions, especially those responsible for healthcare (e.g., provinces, territories, states), need clear processes for incorporating this information into their immunization decision making and program implementation. We interviewed Canadian vaccine experts involved in provincial vaccine policy decision making to identify current practices, perceptions, and recommendations around incorporating economic analysis into that process. Based on these interviews, we make five recommendations: (1) economic evidence should be routinely incorporated into the decision making process; (2) economic experts should sit on, or be available to, regional advisory committees; (3) efforts should be made to build on regional expertise by increasing educational opportunities on economic evaluation; (4) processes should include guidelines for when economic analysis is not required; and (5) clarification on the role of regional advisory groups in economic analysis is needed in relation to national expertise. The information presented here provides a starting point for regional health policy experts and decision makers to work collaboratively with national partners to create transparent and effective approaches to incorporating economic analysis into vaccine decision making.

COVID-19 vaccine uptake and intention during pregnancy in Canada.

OBJECTIVE: To investigate COVID-19 vaccine uptake and intent among pregnant people in Canada, and determine associated factors. METHODS: We conducted a national cross-sectional survey among pregnant people from May 28 through June 7, 2021 (n = 193). Respondents completed a questionnaire to determine COVID-19 vaccine acceptance (defined as either received or intend to receive a COVID-19 vaccine during pregnancy), factors associated with vaccine acceptance, and rationale for accepting/not accepting the vaccine. RESULTS: Of 193 respondents, 57.5% (n = 111) reported COVID-19 vaccine acceptance. Among those who did not accept the vaccine, concern over vaccine safety was the most commonly cited reason (90.1%, n = 73), and 81.7% (n = 67) disagreed with receiving a vaccine that had not been tested in pregnant people. Confidence in COVID-19 vaccine safety (aOR 16.72, 95% CI: 7.22, 42.39), Indigenous self-identification (aOR 11.59, 95% CI: 1.77, 117.18), and employment in an occupation at high risk for COVID-19 exposure excluding healthcare (aOR 4.76, 95% CI: 1.32, 18.60) were associated with vaccine acceptance. Perceived personal risk of COVID-19 disease was not associated with vaccine acceptance in the multivariate model. CONCLUSION: Vaccine safety is a primary concern for this population. Safety information should be communicated to this population as it emerges, along with clear messaging on the benefits of vaccination, as disease risk is either poorly understood or poorly valued in this population.

RéSUMé: OBJECTIF: Examiner l'intention de se faire vacciner contre la COVID-19 et l'adoption du vaccin anti-COVID-19 chez les personnes enceintes au Canada, et déterminer les facteurs associés. MéTHODE: Du 28 mai au 7 juin 2021, nous avons mené un sondage transversal national auprès de personnes enceintes (n = 193). Les répondantes ont rempli un questionnaire pour nous permettre de déterminer l'acceptation du vaccin contre la COVID-19 (définie comme le fait d'avoir reçu ou l'intention de recevoir un vaccin anti-COVID-19 durant la grossesse), les facteurs associés à l'acceptation du vaccin et les motifs d'acceptation ou de refus du vaccin. RéSULTATS: Sur les 193 répondantes, 57,5 % (n = 111) ont dit accepter le vaccin contre la COVID-19. Chez celles qui n'acceptaient pas le vaccin, l'inquiétude face à son innocuité était la raison la plus souvent citée (90,1 %, n = 73), et 81,7 % (n = 67) n'acceptaient pas de recevoir un vaccin qui n'avait pas été testé sur des personnes enceintes. La confiance en l'innocuité du vaccin anti-COVID-19 (RCa 16,72, IC de 95 % : 7,22, 42,39), l'auto-identification en tant que personne autochtone (RCa 11,59, IC de 95 % : 1,77, 117,18) et l'emploi dans une profession à risque élevé d'exposition à la COVID-19, sauf les soins de santé (RCa 4,76, IC de 95 % : 1,32, 18,60) étaient associés à l'acceptation du vaccin. Le risque personnel perçu de tomber malade de la COVID-19 n'était pas associé à l'acceptation du vaccin dans notre modèle multivarié. CONCLUSION: L'innocuité du vaccin est une préoccupation majeure dans cette population. Des informations sur l'innocuité devraient être communiquées aux personnes enceintes au fur et à mesure qu'elles sont connues, ainsi que des messages clairs sur les avantages de la vaccination, car le risque de maladie est soit mal compris, soit déconsidéré dans cette population.

Continuity of routine immunization programs in Canada during the COVID-19 pandemic.

INTRODUCTION: In Canada, the COVID-19 pandemic has interrupted many routine health services, placed additional strain on the health care system, and resulted in many Canadians being either unable or unwilling to attend routine immunization appointments. We sought to capture and synthesize information about changes to routine immunization programs in response to the pandemic and plans to catch-up any missed immunizations. METHODS: Provincial/territorial (P/T) public health leaders were interviewed via teleconference between August-October 2020 to collect information on the following topics: how routine immunization delivery was affected during and after initial lockdown periods, plans to catch-up missed doses, and major challenges and achievements in continuing routine immunization programs. Data were coded and categorized according to common responses and descriptive analysis was performed. RESULTS: Interviews occurred with participants from 11 of 13 P/Ts. School immunization programs were reported to be most negatively affected by the pandemic (n = 9). In the early pandemic period, infant, preschool, and maternal/prenatal programs were prioritized, with most P/Ts continuing these services with adaptations for COVID-19. After the initial lockdown period, all routine programs were continuing with adaptations in most P/Ts. Infant, preschool, and school programs were most often targeted for catch-up through measures such as appointment rebooking and making additional clinics and/or providers available. Major challenges included resource limitations (e.g., staff shortages, PPE shortages, limited infrastructure) (n = 11), public health restrictions (n = 8), and public hesitancy to attend appointments (n = 5). CONCLUSIONS: Canadian routine immunization programs faced some disruptions due to the COVID-19 pandemic, particularly the school, adult, and older adult programs. Further research is needed to determine the measurable impact of the pandemic on routine vaccine coverage levels.

The Emergence of SARS-CoV-2 Variant(s) and Its Impact on the Prevalence of COVID-19 Cases in the Nabatieh Region, Lebanon.

Background: An outbreak of an unknown respiratory illness caused by a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan in Hubei Province, China, in December 2019 and was referred to as coronavirus disease-2019 (COVID-19). Soon after, it was declared as a global pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 mainly infects the respiratory tract with different outcomes ranging from asymptomatic infection to severe critical illness leading to death. Different SARS-CoV-2 variants are emerging of which three have raised concerns worldwide due to their high transmissibility among populations. Objective: To study the prevalence of COVID-19 in the region of Nabatieh-South Lebanon during the past year and assess the presence of SARS-CoV-2 variants and their effect on the spread of infection during times of lockdown. Methods: In our study, 37,474 nasopharyngeal swab samples were collected and analyzed for the detection of SARS-CoV-2 virus in suspected patients attending a tertiary health care center in South Lebanon during the period between 16 March 2020 and 21 February 2021. Results: The results demonstrated a variation in the prevalence rates ranging from less than 1% during full lockdown of the country to 8.4% upon easing lockdown restrictions and reaching 27.5% after the holidays and 2021 New Year celebrations. Interestingly, a new variant(s) appeared starting January 2021 with a significant positive association between the prevalence of positive tests and the percentage of the variant(s). Conclusions: Our results indicate that the lockdown implemented by the Lebanese officials was an effective intervention to contain COVID-19 spread. Our study also showed that lifting lockdown measures during the holidays, which allowed indoor crowded gatherings to occur, caused a surge in COVID-19 cases and rise in the mortality rates nationwide. More importantly, we confirmed the presence of a highly transmissible SARS-CoV-2 variant(s) circulating in the Lebanese community from at least January 2021 onwards.

Environmental scan of provincial and territorial planning for COVID-19 vaccination programs in Canada.

BACKGROUND: Public health departments in Canada are currently facing the challenging task of planning and implementing coronavirus disease 2019 (COVID-19) vaccination programs. OBJECTIVE: To collect and synthesize information regarding COVID-19 vaccination program planning in each province and territory of Canada, including logistic considerations, priority groups, and vaccine safety and effectiveness monitoring. METHODS: Provincial/territorial public health leaders were interviewed via teleconference during the early planning stage of COVID-19 vaccination programs (August-October 2020) to collect information on the following topics: unique factors for COVID-19 vaccination, intention to adopt National Advisory Committee on Immunization (NACI) recommendations, priority groups for early vaccination, and vaccine safety and effectiveness monitoring. Data were grouped according to common responses and descriptive analysis was performed. RESULTS: Eighteen interviews occurred with 25 participants from 11 of 13 provinces/territories (P/Ts). Factors unique to COVID-19 vaccination included prioritizing groups for early vaccination (n=7), public perception of vaccines (n=6), and differing eligibility criteria (n=5). Almost all P/Ts (n=10) reported reliance on NACI recommendations. Long-term care residents (n=10) and healthcare workers (n=10) were most frequently prioritized for early vaccination, followed by people with chronic medical conditions (n=9) and seniors (n=8). Most P/Ts (n=9) are planning routine adverse event monitoring to assess vaccine safety. Evaluation of effectiveness was anticipated to occur within public health departments (n=3), by researchers (n=3), or based on national guidance (n=4). CONCLUSION: Plans for COVID-19 vaccination programs in the P/Ts exhibit some similarities and are largely consistent with NACI guidelines, with some discrepancies. Further research is needed to evaluate COVID-19 vaccination programs once implemented.

Assessment of the skin barrier function in the reconstructed human epidermis using a multimodal approach at molecular, tissue and functional levels.

Reconstructed human epidermis models are used as epidermis alternatives in skin research studies. It is necessary to provide molecular and functional characterization in order to assess these models. Our aim is to establish a link between the barrier function and the structure and composition of the stratum corneum using several complementary techniques. The following three studies were performed on reconstructed human epidermis during the keratinocyte differentiation process: (i) caffeine percutaneous penetration kinetics, (ii) epidermis thickness measurement, stratum corneum formation and lipid organization by Raman microspectroscopy and (iii) lipid composition evolution by liquid chromatography coupled to high-resolution mass spectrometry. The results demonstrated that the caffeine penetration decreased along the differentiation process. Raman in-depth images demonstrated an increase in stratum corneum and RHE thickness accompanied by the evolution of lipid organization. Lipid analysis showed an increase of the ceramide amount and an inverse relationship between ceramide and its precursor levels during the differentiation process. Different behaviors between several ceramide subclasses are highlighted and they relied on the corresponding differentiation stages. The generation of the most important ceramides for the barrier function is closely followed. A period shift between lipid generation and their organization was found. Our analytical data allowed identifying the following 3 groups of maturation days: before day 15, between days 15 and 19, and after day 19. The chemical and physiological states of the barrier function for each group are described thanks to a multimodal approach.

Biomolecular modifications during keratinocyte differentiation: Raman spectroscopy and chromatographic techniques.

From the basal layer until the stratum corneum, lipid and protein biomarkers associated with morphological changes denote keratinocyte differentiation and characterize each epidermis layer. Herein, we followed keratinocyte differentiation in the early stages using HaCaT cells over a period of two weeks by two complementary analytical techniques: Raman microspectroscopy and high-performance liquid chromatography coupled with high resolution mass spectrometry. A high concentration of calcium in the medium induced HaCaT cell differentiation in vitro. The results from both techniques underlined the keratinocyte passage from the granular layer (day 9) to the stratum corneum layer (day 13). After 13 days of differentiation, we observed a strong increase in the lipid content, decrease in proteins, decrease in DNA, and a decrease in glucosylceramides/ceramides and sphingomyelins/ceramides ratios.

Comprehensive characterization and simultaneous analysis of overall lipids in reconstructed human epidermis using NPLC/HR-MSn: 1-O-E (EO) Cer, a new ceramide subclass.

Stratum corneum lipids are responsible for the skin's barrier function. They are the final product of epidermis lipid biosynthesis. During this process, lipids evolve from simple to complex structures in three main levels respectively (stratum basal level, stratum granulosum level, and stratum corneum level). Our aim was to simultaneously analyze and characterize the structure of total epidermis lipids. A powerful analytical method (normal-phase liquid chromatography coupled with high-resolution mass spectrometry (NPLC/HR-MSn)) was developed in order to separate, in a single run, lipid classes with a wide polarity range. Chromatographic conditions were particularly designed to analyze lipids of intermediate polarity such as ceramides. Rich information was obtained about the molecular structure of keratinocyte differentiation biomarkers such as ceramides, glucosylceramides, and sphingomyelins and the microstructures of reconstructed human epidermis lipids using HR-MSn. A new subclass of ceramides, 1-O-Acyl Omega-linoleoyloxy ceramides [1-O-E (EO) Cer] has been highlighted. This class is double esterified on the 1-O-position of sphingoid base with long to very long chain acyl residues (1-O-E) and on the position of ω-hydroxyl group of fatty acid with the linolenic acid (EO). Considering its chemical structure and hydrophobicity, this subclass can contribute to the skin barrier. In addition, we detected a new epidermis sphingomyelins. Our lipidomic approach offers a direct access to epidermis biomarkers.

Long-Term Survival and Echocardiographic Findings After Surgical Ventricular Restoration.

BACKGROUND: This study investigates the long-term survival and durability of mitral procedures on patients undergoing surgical ventricular restoration. METHODS: From 1992 to 2017, 109 patients underwent surgical ventricular restoration. Survival was determined from hospital records and the National Death Index. Preoperative demographics, clinical characteristics and features, operative technique, and follow-up echocardiography findings were analyzed using Cox regression and log-rank to determine variables influencing survival. RESULTS: The mean age was 61.57 ± 12.81 years. There were 101 (93%) true and 8 (7%) pseudo-aneurysms. Concomitant surgeries included mitral valve (MV) repair (n = 40, 37%), MV replacement (n = 5, 5%), tricuspid valve repair (n = 4, 4%), aortic valve replacement (n = 3, 3%), coronary bypass grafting (n = 76, 70%; 1.6 ± 1.3 grafts), and ventricular septal defect closure (n = 5, 5%). Redo-sternotomies were performed in 12 patients (11%). Median duration of echocardiographic follow up was 2.9 years (interquartile range, 9.0) and was obtained in 59 patients (54%). Left ventricular ejection fraction improved from 28% ± 13% to 33% ± 16% (p = 0.011). Median duration of echocardiographic follow-up of MV repair was 3.6 years (interquartile range, 9.5). MV repair led to sustained improvements in mitral regurgitation (MR; p = 0.001) where only 2 (5%) experienced recurrence of moderate to severe MR. For patients who did not undergo an MV procedure there was no difference in preoperative and follow-up MR severity (p = 0.586). Median patient follow-up was 7.1 years (interquartile range, 8.5). Overall 5-, 10-, and 15-year survival rates were 71.9%, 48.1%, and 26.2%, respectively. CONCLUSIONS: Surgical ventricular restoration was associated with sustained improvement in left ventricular ejection fraction with almost half surviving to 10 years postoperatively. For patients undergoing concomitant MV repair, the improvement in mitral competence is durable.

Metabotropic glutamate receptor-1 regulates inflammation in triple negative breast cancer.

Breast cancer remains a major cause of death among women. 15% of these cancers are triple negative breast cancer (TNBC), an aggressive subtype of breast cancer for which no current effective targeted therapy exists. We have previously demonstrated a role for mGluR1 in mediating tumor cell growth, endothelial cell proliferation, and tumor-induced angiogenesis in TNBC. In this study, we explore a role for mGluR1 in regulating inflammation in TNBC. GRM1 expression was silenced in MDA-MB-231 cells to study changes in expression of inflammatory genes regulated by mGluR1. Results were confirmed by ELISA using GRM1-silenced and overexpressed cells and mGluR1 inhibitors. A functional role for these differentially expressed genes was determined in vitro and in vivo. 131 genes were differentially expressed in GRM1-silenced MDA-MB-231 cells, with some of these falling into four major canonical pathways associated with acute inflammation, specifically leukocyte migration/chemotaxis. Upregulation of three of these genes (CXCL1, IL6, IL8) and their corresponding protein was confirmed by qPCR analysis and ELISA in GRM1-manipulated TNBC cells. Upregulation of these cytokines enhanced endothelial adhesion and transmigration of neutrophils in co-culture assays and in 4T1 mouse tumors. Our results suggest mGluR1 may serve as a novel endogenous regulator of inflammation in TNBC.