A multinational Delphi consensus to end the COVID-19 public health threat.

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

A global action agenda for turning the tide on fatty liver disease.

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Molecular mechanisms of postoperative atrial fibrillation in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) promotes atrial remodeling and fibrosis, providing a substrate for atrial fibrillation (AF). Herein, we investigate the pathophysiological mechanisms of AF in association with OSA in a cohort of cardiac surgery patients. A prospective study including patients undergoing cardiac surgery. Biomarkers reflective of AF pathophysiology (interleukin [IL-6], C-reactive protein [CRP], von Willebrand factor [vWF], N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity Troponin T [hs-TnT], and Galectin-3 [Gal-3]) was assessed by functional or immunological assays. miRNAs involved in AF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Using atrial tissue samples, fibrosis was assessed by Masson's trichrome. Connexin 40 and 43 (Cx40; Cx43) were evaluated by immunolabeling. Fifty-six patients (15 with OSA and 41 non-OSA) were included in this hypothesis-generating pilot study. OSA group had a higher incidence of postoperative AF (POAF) (46.7% vs. 19.5%; p = .042), presented an increased risk of POAF (OR 3.61, 95% CI 1.01-12.92), and had significantly higher baseline levels of NT-proBNP (p = .044), vWF (p = .049), Gal-3 (p = .009), IL-6 (p = .002), and CRP (p = .003). This group presented lower levels of miR-21 and miR-208 (both p < .05). Also, lower Cx40 levels in POAF and/or OSA patients (50.0% vs. 81.8%, p = .033) were found. The presence of interstitial fibrosis (according to myocardial collagen by Masson's trichrome) was raised in OSA patients (86.7% vs. 53.7%, p = .024). Several biomarkers and miRNAs involved in inflammation and fibrosis were dysregulated in OSA patients, which together with a higher degree of interstitial fibrosis, altered miRNA, and Cxs expression predisposes to the development of a substrate that increases the AF risk.

Chemical Multiverse and Diversity of Food Chemicals.

Food chemicals have a fundamental role in our lives, with an extended impact on nutrition, disease prevention, and marked economic implications in the food industry. The number of food chemical compounds in public databases has substantially increased in the past few years, which can be characterized using chemoinformatics approaches. We and other groups explored public food chemical libraries containing up to 26,500 compounds. This study aimed to analyze the chemical contents, diversity, and coverage in the chemical space of food chemicals and additives and, from here on, food components. The approach to food components addressed in this study is a public database with more than 70,000 compounds, including those predicted via omics techniques. It was concluded that food components have distinctive physicochemical properties and constitutional descriptors despite sharing many chemical structures with natural products. Food components, on average, have large molecular weights and several apolar structures with saturated hydrocarbons. Compared to reference databases, food component structures have low scaffold and fingerprint-based diversity and high structural complexity, as measured by the fraction of sp3 carbons. These structural features are associated with a large fraction of macronutrients as lipids. Lipids in food components were decompiled by an analysis of the maximum common substructures. The chemical multiverse representation of food chemicals showed a larger coverage of chemical space than natural products and FDA-approved drugs by using different sets of representations.

A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.

Physician engagement in reproductive health advocacy: findings from a mixed methods evaluation of a leadership and advocacy program.

BACKGROUND: Medical curricula include advocacy competencies, but how much physicians engage in advocacy and what enables this engagement is not well characterized. The authors assessed facilitators and barriers to advocacy identified by physician alumni of a reproductive health advocacy training program. METHODS: The authors present secondary results from a mixed methods program evaluation from 2018 to 2020, using alumni data from a cross-sectional survey (n = 231) and in-depth interviews (IDIs, n = 36). The survey measured engagement in policy, media, professional organization, and medical education advocacy and the value placed on the community fostered by the program (eight questions, Cronbach's alpha = 0.81). The authors estimated the association of community value score with advocacy engagement using multivariable Poisson regression to estimate prevalence ratios and analyzed IDI data inductively. RESULTS: Over one third of alumni were highly engaged in legislative policy (n = 90, 39%), professional organizations (n = 98, 42%), or medical education (n = 89, 39%), with fewer highly active in media-based advocacy (n = 54, 23%) in the year prior to the survey. Survey and IDI data demonstrated that passion, sense of urgency, confidence in skills, and the program's emphasis on different forms of advocacy facilitated engagement in advocacy, while insufficient time, safety concerns, and sense of effort redundancies were barriers. The program community was also an important facilitator, especially for "out loud" efforts and for those working in environments perceived as hostile to abortion care (e.g., alumni in hostile environments with high community value scores were 1.8 times [95% CI 1.3, 2.6] as likely to report medium/high levels of media advocacy compared to those with low scores after adjusting for age, gender, and clinical specialty). CONCLUSION: Physician advocacy training curricula should include both skills- and community-building and identify a full range of forms of advocacy. Community-building is especially important for physician advocacy for reproductive health services such as abortion care.

Effective and alternative treatment of anastomotic leak after gastrojejunal bypass: endoluminal vacuum therapy.

Anastomotic leak (AL) after with Roux-en-Y gastric bypass (RYGB) has a morbidity rate to 53% and it can be potentially lethal (mortality rate from 0.5 to 10%). In these cases, surgery is usually a challenge, so in recent years minimally invasive endoscopic treatment is gaining ground. Endoluminal vacuum therapy (EVAC) is a promising treatment that is being used in esophagogastric and rectal surgery for the management of AL. We present the case of a patient on his 5th postoperative day of bariatric surgery (RYGB) with an acute abdomen. He was diagnosed of dehiscence of gastrojejunal anastomosis and he needed urgent surgery twice. Subsequently, in control CT, a new anastomotic leak is evidenced. However, given the clinical stability of the patient, it was decided to start EVAC type ESO-Sponge® placed by endoscopy. A total of 4 changes are made every 3-4 days with a total duration of treatment of 15 days. EVAC was removed when the defect presented a 1 mm sized.

A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.

A global research priority agenda to advance public health responses to fatty liver disease.

BACKGROUND & AIMS: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. METHODS: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. RESULTS: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had <80% 'agree', with greater reliance on 'somewhat agree' to achieve >90% combined agreement. CONCLUSIONS: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. IMPACT AND IMPLICATIONS: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.

Approaches to Research Ethics in Health Research on YouTube: Systematic Review.

BACKGROUND: YouTube has become a popular source of health care information, reaching an estimated 81% of adults in 2021; approximately 35% of adults in the United States have used the internet to self-diagnose a condition. Public health researchers are therefore incorporating YouTube data into their research, but guidelines for best practices around research ethics using social media data, such as YouTube, are unclear. OBJECTIVE: This study aims to describe approaches to research ethics for public health research implemented using YouTube data. METHODS: We implemented a systematic review of articles found in PubMed, SocINDEX, Web of Science, and PsycINFO following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. To be eligible to be included, studies needed to be published in peer-reviewed journals in English between January 1, 2006, and October 31, 2019, and include analyses on publicly available YouTube data on health or public health topics; studies using primary data collection, such as using YouTube for study recruitment, interventions, or dissemination evaluations, were not included. We extracted data on the presence of user identifying information, institutional review board (IRB) review, and informed consent processes, as well as research topic and methodology. RESULTS: This review includes 119 articles from 88 journals. The most common health and public health topics studied were in the categories of chronic diseases (44/119, 37%), mental health and substance use (26/119, 21.8%), and infectious diseases (20/119, 16.8%). The majority (82/119, 68.9%) of articles made no mention of ethical considerations or stated that the study did not meet the definition of human participant research (16/119, 13.4%). Of those that sought IRB review (15/119, 12.6%), 12 out of 15 (80%) were determined to not meet the definition of human participant research and were therefore exempt from IRB review, and 3 out of 15 (20%) received IRB approval. None of the 3 IRB-approved studies contained identifying information; one was explicitly told not to include identifying information by their ethics committee. Only 1 study sought informed consent from YouTube users. Of 119 articles, 33 (27.7%) contained identifying information about content creators or video commenters, one of which attempted to anonymize direct quotes by not including user information. CONCLUSIONS: Given the variation in practice, concrete guidelines on research ethics for social media research are needed, especially around anonymizing and seeking consent when using identifying information. TRIAL REGISTRATION: PROSPERO CRD42020148170; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148170.

Ethical and Methodological Considerations of Twitter Data for Public Health Research: Systematic Review.

BACKGROUND: Much research is being carried out using publicly available Twitter data in the field of public health, but the types of research questions that these data are being used to answer and the extent to which these projects require ethical oversight are not clear. OBJECTIVE: This review describes the current state of public health research using Twitter data in terms of methods and research questions, geographic focus, and ethical considerations including obtaining informed consent from Twitter handlers. METHODS: We implemented a systematic review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, of articles published between January 2006 and October 31, 2019, using Twitter data in secondary analyses for public health research, which were found using standardized search criteria on SocINDEX, PsycINFO, and PubMed. Studies were excluded when using Twitter for primary data collection, such as for study recruitment or as part of a dissemination intervention. RESULTS: We identified 367 articles that met eligibility criteria. Infectious disease (n=80, 22%) and substance use (n=66, 18%) were the most common topics for these studies, and sentiment mining (n=227, 62%), surveillance (n=224, 61%), and thematic exploration (n=217, 59%) were the most common methodologies employed. Approximately one-third of articles had a global or worldwide geographic focus; another one-third focused on the United States. The majority (n=222, 60%) of articles used a native Twitter application programming interface, and a significant amount of the remainder (n=102, 28%) used a third-party application programming interface. Only one-third (n=119, 32%) of studies sought ethical approval from an institutional review board, while 17% of them (n=62) included identifying information on Twitter users or tweets and 36% of them (n=131) attempted to anonymize identifiers. Most studies (n=272, 79%) included a discussion on the validity of the measures and reliability of coding (70% for interreliability of human coding and 70% for computer algorithm checks), but less attention was paid to the sampling frame, and what underlying population the sample represented. CONCLUSIONS: Twitter data may be useful in public health research, given its access to publicly available information. However, studies should exercise greater caution in considering the data sources, accession method, and external validity of the sampling frame. Further, an ethical framework is necessary to help guide future research in this area, especially when individual, identifiable Twitter users and tweets are shared and discussed. TRIAL REGISTRATION: PROSPERO CRD42020148170; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=148170.

The Role of COVID-19, Race and Social Factors in Pregnancy Experiences in New York State: The CAP Study.

Given that New York State's (NYS) was the first epicenter of the COVID-19 pandemic in the United States (US), we were interested in potential racial/ethnic differences in pregnancy-related experiences among women pregnant during versus prior to the pandemic. We surveyed 1,525 women (18-44 years) proportionate to geographic and sociodemographic distribution between June 9, 20 and July 21, 20. We carried out bivariate analysis of various social and pregnancy-related factors by racial/ethnic identity (White, Black, Hispanic) and binary logistic and linear regression assessing the association between race/ethnicity, pregnancy prior to/during the pandemic, demographic characteristics, health and social wellbeing, and employment as an essential worker with pregnancy-related healthcare delays and changes. Overall, Black and Hispanic women were significantly more likely to experience a host of negative prenatal and postpartum experiences. In general, multivariate analyses revealed that individuals who were pregnant during the pandemic, lived in NYC, participated in social welfare programs, lacked health insurance, and/or were essential workers were more likely to report delays in prenatal and postpartum care and/or more changes/negative experiences. In light of previous evidence of racial disparities in birth experiences, the higher rates of negative pregnancy/birth-care and postpartum/newborn-care experiences among Black and Hispanic women in bivariate analysis warrant further inspection given that their aggregation for multivariate analysis may have obscured differences at the level of individual events. Findings support continued efforts for universal health insurance and improved social welfare programs. Guidelines are needed to protect essential workers' access to health services, particularly related to pregnancy given the time-sensitive nature of this care.Supplemental data for this article is available online at https://doi.org/10.1080/08964289.2021.1997893 .

Sexual and Reproductive Health Advocacy Successes, Failures, and Needs in the United States: Perspectives From Key Stakeholders.

Physician advocates for sexual and reproductive health (SRH) care have been active in the United States for decades. Despite such activism, access to SRH services has been fraught with persistent restrictions, particularly for abortion care. We sought the perspectives of key stakeholders on what makes for an effective SRH physician advocate and thoughts about the successes, failures, and needs of the abortion advocacy movement. We interviewed 15 SRH key informants (KIs) in sectors with expertise in organizational policy and advocacy (n = 6); clinical leadership and education (n = 3), media (n = 3), and reproductive justice (n = 3). The analytic team coded repeating ideas and conducted a thematic analysis, organizing findings within KI perspectives on the role of physician advocates in the field of abortion and contraception; successes, failures, and needs in abortion and contraception advocacy; and recommendations on the composition and components of an ideal clinician advocacy training program. KIs relayed that skill building related to communication, developing relationships with changemakers, and understanding political systems was critical for effective advocacy. They felt clinician advocacy training programs should include providers other than physicians and be designed for trainees to build relationships with one another over time. KI perspectives can be valuable in informing advocacy training programs and for contributing strategic approaches to increasing equitable and widespread access to SRH services.

Examining Women's and Men's Ideal Criteria Before Forming Families.

In the United States, family formation decision-making is more complex than the predominant models that have been used to capture this phenomenon. Understanding the context in which a pregnancy occurs requires a more nuanced examination. In-depth interviews were conducted with 60 men and women, aged 18-35, who had children or were pregnant. Using grounded theory analysis, themes emerged that revealed participants' ideal criteria desired before pregnancy. We stratified by those who met and did not meet these criteria. Almost universally, participants shared ideal criteria: to graduate, gain financial stability, establish a relationship, and then become pregnant. Many participants did not accomplish these goals. Those who had not met their criteria had experienced traumatic childhoods and suffered economic concerns. For this group, having children prompted positive changes within their control, but financial stability remained limited. Efforts should focus on improving circumstances for all individuals to fulfill their criteria before pregnancy.

Iron availability and oxygen tension regulate the Yersinia Ysc type III secretion system to enable disseminated infection.

The enteropathogen Yersinia pseudotuberculosis and the related plague agent Y. pestis require the Ysc type III secretion system (T3SS) to subvert phagocyte defense mechanisms and cause disease. Yet type III secretion (T3S) in Yersinia induces growth arrest and innate immune recognition, necessitating tight regulation of the T3SS. Here we show that Y. pseudotuberculosis T3SS expression is kept low under anaerobic, iron-rich conditions, such as those found in the intestinal lumen where the Yersinia T3SS is not required for growth. In contrast, the Yersinia T3SS is expressed under aerobic or anaerobic, iron-poor conditions, such as those encountered by Yersinia once they cross the epithelial barrier and encounter phagocytic cells. We further show that the [2Fe-2S] containing transcription factor, IscR, mediates this oxygen and iron regulation of the T3SS by controlling transcription of the T3SS master regulator LcrF. IscR binds directly to the lcrF promoter and, importantly, a mutation that prevents this binding leads to decreased disseminated infection of Y. pseudotuberculosis but does not perturb intestinal colonization. Similar to E. coli, Y. pseudotuberculosis uses the Fe-S cluster occupancy of IscR as a readout of oxygen and iron conditions that impact cellular Fe-S cluster homeostasis. We propose that Y. pseudotuberculosis has coopted this system to sense entry into deeper tissues and induce T3S where it is required for virulence. The IscR binding site in the lcrF promoter is completely conserved between Y. pseudotuberculosis and Y. pestis. Deletion of iscR in Y. pestis leads to drastic disruption of T3S, suggesting that IscR control of the T3SS evolved before Y. pestis split from Y. pseudotuberculosis.

Inhibition of enzymes involved in collagen cross-linking reduces vascular smooth muscle cell calcification.

Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by high-phosphate medium (HPM) conditioning. HPM promoted ECM calcification and up-regulated osteoblast markers associated with induction of LOX and PLOD1 expression and with an increase in ECM-insoluble collagen deposition. Murine VSMCs from transgenic mice overexpressing LOX (TgLOX) exhibited an increase in HPM-dependent calcification and osteoblast commitment compared with wild-type cells. Similarly, enhanced HPM-induced calcification was detected in aorta from TgLOX. Conversely, ß-aminopropionitrile (a LOX inhibitor) and LOX knockdown abrogated VSMC calcification and transdifferentiation. We found a significant positive association between LOX expression and vascular calcification in human atherosclerotic lesions. Likewise, 2,2'-dipyridil (a PLOD inhibitor) and PLOD1 knockdown impaired HPM-induced ECM mineralization and osteoblast commitment. Our findings identify LOX and PLOD as critical players in vascular calcification and highlight the importance of ECM remodeling in this process.-Jover, E., Silvente, A., Marín, F., Martínez-González, J., Orriols, M., Martinez, C. M., Puche, C. M., Valdés, M., Rodriguez, C., Hernández-Romero, D. Inhibition of enzymes involved in collagen cross-linking reduces vascular smooth muscle cell calcification.

A qualitative assessment of perspectives on getting pregnant: the Social Position and Family Formation study.

BACKGROUND: Intentions-oriented approaches to measuring pregnancy do not necessarily align with how people view and approach pregnancy. Our objective was to obtain an in-depth understanding of the notions women and men hold regarding pregnancy. METHODS: We conducted semi-structured in-depth interviews with 176 heterosexual women and men ages 18-35, in the United States. Data were analyzed using grounded theory methodology. RESULTS: Participants described notions of getting pregnant in one of three ways. One group of participants used language that solely described pregnancy as a deliberate process, either premeditated or actively avoided. Another described pregnancy as a predetermined phenomenon, due to fate or something that 'just happens.' The third group represented a blending of both notions. CONCLUSIONS: Our findings underscore the need to shift the current paradigm of deliberate intentions to one that recognizes that pregnancy can also be viewed as predetermined. These findings can be used to improve measurement, health services, and better direct public health resources.

Combined determination of B-type natriuretic peptide and high-sensitivity troponin I in the postmortem diagnosis of cardiac disease.

Cardiac disease is the most common cause of sudden death in Western countries. It is known that high-sensitivity troponin I (hs-cTnI), widely used for detection of myocardial injury, is a sensitive biochemical marker. B-type natriuretic peptide (BNP) is a reliable tool for diagnosing heart failure, and for establishing prognosis or disease severity. We aimed to evaluate the diagnostic efficacy of the postmortem determination of BNP in serum alone or in addition to other biomarkers, such as hs-cTnI and MB isoenzyme of creatine kinase (CK-MB), to ascertain whether its determination improves the post-mortem diagnosis of heart failure-associated causes of death. This study involved 133 cadavers with a mean age of 58.2 (± 17.6) years and a mean postmortem interval of 12.8 (±6.6) h. Cases were assigned into two diagnostic groups, according to the cause of death: cardiac deaths (N = 62) and control (N = 71). In the cardiac group, two categories were established according to morphological features of the heart: 'ischemic deaths' (N = 39), and 'congestive heart' (n = 23). Both hs-cTnI and BNP were useful in diagnosing cardiac deaths, whereas CK-MB did not have any diagnostic relevance. hs-cTnI is higher in cases which acute ischemia as the principal pathology, while the presence of high BNP values is significantly related with chronic cardiac situations with significant ventricular overload. Our findings show that postmortem determination of hs-cTnI and BNP provides valuable information; hs-cTnI is useful for diagnosis of cardiac deaths, mainly with ischemic implications, and BNP gave better results for the diagnosis of congestive heart failure.

Posterior cortical atrophy: a single case cognitive and radiological follow-up.

Posterior cortical atrophy (PCA) is a rare neurodegenerative syndrome characterized by initial predominant visuoperceptual deficits followed by a progressive decline in other cognitive functions. This syndrome has not been as thoroughly described as other dementias, particularly from a neuropsychological evolution perspective with only a few studies describing the evolution of its cognitive progression. In this investigation we review the literature on this rare condition and we perform a 7-year neuropsychological and neuroradiological follow-up of a 64-year-old man with PCA. The subject's deficits initially appeared in his visuoperceptual skills with later affectation appearing in language and other cognitive functions, this being coherent with the patient's parieto-temporal atrophy evolution.