Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). ...We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients.
Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness BWH RoCI, n = 200 and Molecular Epidemiology of Acute Respiratory Distress Syndrome ME ARDS, n = 243). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio OR 7.5, 95% CI 3.6-15.8, p = 1×10(-7)) and ME ARDS (OR 8.4, 95% CI 2.9-24.2, p = 9×10(-5)) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10(-4)) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers.
Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care ...unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients. Methods and Findings Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women's Hospital Registry of Critical Illness BWH RoCI, n = 200 and Molecular Epidemiology of Acute Respiratory Distress Syndrome ME ARDS, n = 243). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio OR 7.5, 95% CI 3.6-15.8, p = 1×10-7) and ME ARDS (OR 8.4, 95% CI 2.9-24.2, p = 9×10-5) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10-4) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers. Conclusions Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors' Summary
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little is known about intimate partner violence-related fatalities among young people. This study comprehensively identifies and describes intimate partner violence-related homicides, ...homicide–suicides, legal intervention deaths, and suicides among young people.
Data from the 2014–2018 National Violent Death Reporting System were analyzed for all decedents aged 0–24 years in 38 states, the District of Columbia, and Puerto Rico with known circumstances of death (n=29,702). Intimate partner violence-related deaths were identified using National Violent Death Reporting System variables across all manners of death and supplementary narrative review for suicides. This article reports the proportion of intimate partner violence versus non–intimate partner violence-related deaths by manner of death, descriptive statistics, and rate of intimate partner violence-related death per 100,000 person years. To examine disparities in intimate partner violence-related deaths, generalized estimating equations were used with robust standard errors to account for clustering of deaths within states and fixed effects for years. Statistical analyses were conducted May and August 2021.
A total of 1,927 intimate partner violence-related deaths were identified, which represents 6.5% of violent deaths with known circumstances, at a rate of 0.35 per 100,000 person years. Supplementary narrative review identified 44.7% of all intimate partner violence-related deaths. There were significant differences by race/ethnicity and whether a firearm inflicted the fatal injury for male and female decedents by manner of death.
If the National Violent Death Reporting System does not assess whether intimate partner violence was a precipitating factor across all death manners, the true magnitude of intimate partner violence's contribution to violent death will be underestimated. Future research that identifies factors associated with all manners of intimate partner violence-related deaths among young people will help inform intervention and prevention strategies to save young lives.
Antarctic sea ice plays a critical role in the Earth system, influencing energy, heat and freshwater fluxes, air-sea gas exchange, ice shelf dynamics, ocean circulation, nutrient cycling, marine ...productivity and global carbon cycling. However, accurate simulation of recent sea-ice changes remains challenging and, therefore, projecting future sea-ice changes and their influence on the global climate system is uncertain. Reconstructing past changes in sea-ice cover can provide additional insights into climate feedbacks within the Earth system at different timescales. This paper is the first of two review papers from the Cycles of Sea Ice Dynamics in the Earth system (C-SIDE) working group. In this first paper, we review marine- and ice core-based sea-ice proxies and reconstructions of sea-ice changes throughout the last glacial-interglacial cycle.
Objectives
The Holocene arrival of humans on Madagascar precipitated major changes to the island's biodiversity. The now‐extinct, endemic “subfossil” megafauna of Madagascar were likely hunted by ...early human inhabitants. Perhaps in part due to preferential hunting of larger prey, no surviving endemic species on Madagascar is >10 kg. Moreover, some subfossil bones of extant lemurs are considerably larger than those of the modern members of their species, but subfossil versus modern locale differences for the comparisons conducted to date lead to uncertainty about whether these size differences reflect in situ change or pre‐existing ecogeographic variation. Here, we revisited this question with samples from nearby locales.
Materials and Methods
We used high‐resolution 3D scan data to conduct comparative morphological analyses of subfossil and modern skeletal remains of one of the larger extant lemurs, Verreaux's sifakas (Propithecus verreauxi) from subfossil and modern sites only ~10 km apart: Taolambiby (bones dated to 725–560—1075–955 cal. years before present) and Beza Mahafaly Special Reserve, respectively.
Results
The mean aggregate score for all subfossil elements (n = 12; 0.089 ± 0.117) is significantly greater than that for the modern individuals (n = 31; 0.009 ± 0.045; t‐test; p = 0.039). We found that the average subfossil sifaka bone is ~9% larger than that of modern sifakas (permutation test p = 0.037).
Discussion
We cannot yet conclude whether this size difference reflects evolutionary change or an archaeological aggregation/taphonomic process. However, if this is a case of phyletic dwarfism in response to human size‐selective harvesting pressures then the estimated rate of change is greater than those previously calculated for other archaeological cases of this phenomenon.
We evaluated potential changes in Propithecus verreauxi body size in a single region of Magadagascar since the earliest indications of human hunting activities in the area. Our analysis indicated that the average aggregate scores of subfossil femoral and humeral bone measurements were larger than modern bone measurements.
Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to ...reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.
Le traitement antiplaquettaire est la base du traitement et de la prévention des manifestations athérothrombotiques chez les patients atteints d’une maladie cardiovasculaire athéroscléreuse. Le choix du traitement antiplaquettaire approprié pour réduire les événements cardiovasculaires indésirables majeurs, tout en tenant compte du risque de saignement, demande un suivi constant des essais cliniques. En annexe, la mise à jour ciblée des lignes directrices de la Société cardiovasculaire du Canada/Association canadienne de cardiologie d’intervention pour l’utilisation du traitement antiplaquettaire formule des recommandations sur les sujets suivants : 1) l’emploi de l’acide acétylsalicylique dans la prévention primaire des maladies cardiovasculaires athéroscléreuses; 2) la durée de la bithérapie antiplaquettaire après une intervention coronarienne percutanée (ICP) chez les patients qui présentent un risque élevé de saignement; 3) le choix d’une bithérapie antiplaquettaire puissante (inhibiteur de P2Y12) chez les patients qui présentent un syndrome coronarien aigu et les stratégies éventuelles de désescalade de la bithérapie antiplaquettaire après une ICP; 4) le choix et la durée de la bithérapie antiplaquettaire chez les patients atteints du syndrome coronarien aigu qui reçoivent un traitement médical sans revascularisation; 5) le prétraitement par une bithérapie antiplaquettaire (inhibiteur de P2Y12) avant une coronarographie non urgente ou urgente; 6) la prise en charge par un traitement antiplaquettaire périopératoire et à long terme chez les patients qui ont besoin d’un pontage aortocoronarien; et 7) l’utilisation du traitement antiplaquettaire chez les patients qui présentent une fibrillation auriculaire et qui ont besoin d’un traitement anticoagulant par voie orale après une ICP ou qui présentent un syndrome coronarien aigu traité médicalement. Toutes les recommandations reposent sur les analyses des publications et les méta-analyses menées dans le but de formuler ces lignes directrices, fournies dans le matériel supplémentaire.
Inhalation profiles to support use of dry powder inhalers for drug delivery in patients with pulmonary arterial hypertension have not been reported. We aimed to evaluate the inspiratory flow pattern ...associated with low and medium flow resistance dry powder inhaler devices (RS01-L and RS01-M, respectively) in patients with pulmonary arterial hypertension. This single-center study enrolled patients with pulmonary arterial hypertension associated with connective tissue disease (n = 10) and idiopathic pulmonary arterial hypertension (n = 10) to measure the following inhalation parameters: inspiratory effort (kPa), peak inspiratory flow rate (L/min), inhaled volume (L), and flow increase rate (L/s2) using the two devices. We identified a trend toward higher mean pulmonary artery pressure in the idiopathic pulmonary arterial hypertension group (50 ± 13 mmHg vs. 40 ± 11 mmHg in pulmonary arterial hypertension associated with connective tissue disease; p = 0.077). On average, peak inspiratory flow rate was higher with RS01-L vs. RS01-M (84 ± 19.7 L/min vs. 70.4 ± 13.2 L/min; p = 0.015). In the overall group, no differences between RS01-L and RS01-M were observed for inhaled volume, inspiratory effort, or flow increase rate. Inhaled volume with RS01-L was higher in pulmonary arterial hypertension associated with connective tissue disease vs. idiopathic pulmonary arterial hypertension patients: 1.6 ± 0.4 L vs. 1.3 ± 0.2 L; p = 0.042. For the RS01-L, inhaled volume correlated with forced expiratory volume in one second (r = 0.460, p = 0.030) and forced vital capacity (r = 0.507, p = 0.015). In patients with pulmonary arterial hypertension associated with connective tissue disease using RS01-L, both inspiratory effort and flow increase rate were highly correlated with pulmonary vascular compliance (r = 0.903, p = 0.0001 and r = 0.906, p = 0.0001; respectively); while with RS01-M, inspiratory effort was highly correlated with pulmonary vascular compliance (r = 0.8, p = 0.001). Our data suggest that the use of RS01-L and RS01-M dry powder inhaler devices allowed adequate inspiratory flow in pulmonary arterial hypertension patients. The correlation between flow increase rate and pulmonary vascular compliance in pulmonary arterial hypertension associated with connective tissue disease deserves further investigation.
ABSTRACT
Selma Fraiberg's pioneering work with infants, toddlers, and families over 40 years ago led to the development of a field in which professionals from multiple disciplines learned to work ...with or on behalf of infants, very young children, their parents, and the relationships that bind them together. The intent was to promote social and emotional health through enhancing the security of early developing parent–child relationships in the first years of life (Fraiberg, 2018). Called infant mental health (IMH), practitioners from fields of health, education, social work, psychology, human development, nursing, pediatrics, and psychiatry specialize in supporting the optimal development of infants and the developing relationship between infants and their caregivers. When a baby is born into optimal circumstances, to parents free of undue economic and psychological stressors and who are emotionally ready to provide care and nurturing for an infant's needs, an IMH approach may be offered as promotion or prevention, with the goal of supporting new parent(s) in developing confidence in their capacity to understand and meet the needs of the tiny human they are coming to know and care for. However, when parental history is fraught with abandonment, loss, abuse or neglect, or the current environment is replete with economic insecurity, threats to survival due to interpersonal or community violence, social isolation, mental illness, or substance abuse, the work of the IMH therapist may require intervention or intensive treatment and becomes more psychotherapeutic in nature. The underlying therapeutic goal is to create a context in which the baby develops within the environment of a parent's nurturing care without the psychological impingement that parental history of trauma or loss or current stressors such as isolation, poverty, or the birth of a child with special needs, can incur.
•Used survival analysis to see impact of maternal factors on program attrition.•Higher retention in infant mental health home visiting program for depressed moms.•Higher attrition in home visiting ...program for younger and less educated moms.•Cumulative factors related to inequality were strongest predictor of attrition.•Cumulative mental health problems were predictive of longer retention.
Home visiting programs are prominent prevention and intervention models that improve the well-being of infants, young children and their families who are at risk for negative outcomes. However, many home visiting programs struggle to retain families for the length of the intervention. We used survival analysis to examine the impact of demographic (e.g., education, socioeconomic status) and mental health concerns (e.g., maternal stress, therapist-rated mental health status) factors on the retention of 70 mothers in Infant Mental Health-Home Visiting (IMH-HV), a multi-faceted, needs-driven, relationship-focused psychotherapeutic home visiting model. The impact of both individual and cumulative factors on retention was examined. Results revealed that shorter retention in treatment was predicted by younger maternal age at the time of childbirth, lower levels of education, and an accumulation of demographic characteristics often reflecting structural inequalities. In contrast, mental health concerns, depression in particular, predicted longer retention. For each additional structural inequity, the risk of leaving treatment increased by 60%. For each additional mental health concern, the risk of leaving treatment decreased by 25%. The findings regarding structurally-driven inequities are consistent with much of the previous research. In contrast, the finding that those with a higher composite mental health score were more likely to remain in treatment longer than those with lower levels is counter to many studies. These results may be partially explained by the mental health and relational focus of the Michigan model of IMH-HV.
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