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Adverse pregnancies outcomes present a clinical dilemma in Perinatal medicine. This is partly due to lack of accuracy of current biomarkers to predict high-risk pregnancies at an earlier stage. The placental alkaline phosphatase (PLAP) carrying extracellular vesicles (EVs), and their cargo have been reported as a source of biomarkers for placental health and an indication of pre-eclampsia progression. We postulate that PLAP is not only placental but also expressed in other fetal organs, suggesting that PLAP + ve EVs are not only a functional indicator of placental function alone. We evaluated PLAP in the placenta, fetal membranes, maternal decidua, myometrial cells, and the EVs derived from them. Various bioanalytical techniques were used to detect PLAP expressions in the cells and EVs. The EVs were characterized by size/quantity, PLAP as a cargo, and canonical EV protein markers. PLAP expression was determined in the chorion trophoblast cells (CTCs) of the fetal membranes and the placental trophoblasts; however, it was absent in the amnion layer of the fetal membranes and the maternal uterine cells used in this study. Using multiple experimental approaches, we further verified the cellular sources of PLAP and confirmed that the EVs from the chorion and placental trophoblasts contain PLAP. Our studies suggest that PLAP is not truly placental. Instead, cells of trophoblast lineage in both fetal membranes and the placenta express PLAP in cells and their EVs. Although PLAP + ve EVs for biomarkers are not exclusively placental, they still represent real-time fetal-specific tissues conditions during pregnancy. • PLAP carrying EVs cannot be considered as placental origin. • The cells of trophoblast lineage in both fetal membranes and the placenta express PLAP in cells and their EVs. • Maternal upper and lower uterine cells do not express PLAP and the EVs are negative for PLAP. [ABSTRACT FROM AUTHOR]

The pathophysiology of Crohn's-like disease of the pouch (CDP) in patients with a history of ulcerative colitis (UC) is unknown. We examined mucosal cells from patients with and without CDP using single-cell analyses. Endoscopic samples were collected from pouch body and prepouch ileum (pouch/ileum) of 50 patients with an ileal pouch-anal anastomosis. Single-cell RNA sequencing was performed on pouch/ileal tissues of patients with normal pouch/ileum and CDP. Mass cytometry was performed on mucosal immune cells from patients with UC with normal pouch/ileum, CDP, pouchitis, and those with familial adenomatous polyposis after pouch formation. Findings were independently validated using immunohistochemistry. The cell populations/states in the pouch body differed from those in the prepouch ileum, likely secondary to increased microbial burden. Compared with the familial adenomatous polyposis pouch, the UC pouch was enriched in colitogenic immune cells even without inflammation. CDP was characterized by increases in T helper 17 cells, inflammatory fibroblasts, inflammatory monocytes, TREM1+ monocytes, clonal expansion of effector T cells, and overexpression of T helper 17 cells–inducing cytokine genes such as IL23 , IL1B , and IL6 by mononuclear phagocytes. Ligand-receptor analysis further revealed a stromal-mononuclear phagocytes-lymphocyte circuit in CDP. Integrated analysis showed that up-regulated immune mediators in CDP were similar to those in CD and pouchitis, but not UC. Additionally, CDP pouch/ileum exhibited heightened endoplasmic reticulum stress across all major cell compartments. CDP likely represents a distinct entity of inflammatory bowel disease with heightened endoplasmic reticulum stress in both immune and nonimmune cells, which may become a novel diagnostic biomarker and therapeutic target for CDP. [Display omitted] The pathophysiology of Crohn's-like disease of the pouch in patients with a prior history of ulcerative colitis is revealed and new targets to better treat this challenging condition are identified. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? What is the accuracy of DeltaScan; a portable brain state monitor that offers real-time automated artifact rejection and analysis, delivering a probability score for both acute encephalopathy and delirium in both ICU and non-ICU patients? • What is the main finding of this study? The device can detect acute encephalopathy and delirium with good discrimination statistics especially in older patients, regardless of their postoperative state, psycho-active medication use, or prior psychiatric history. • What is the meaning of the finding? The study suggests that the DeltaScan could be a valuable tool for improving delirium monitoring practices, given that delirium is often overlooked, difficult to differentiate from other psychiatric disorders, and current questionnaire-based monitoring tools suffer from inter-rater variability. To measure the diagnostic accuracy of DeltaScan: a portable real-time brain state monitor for identifying delirium, a manifestation of acute encephalopathy (AE) detectable by polymorphic delta activity (PDA) in single-channel electroencephalograms (EEGs). Prospective cross-sectional study. Six Intensive Care Units (ICU's) and 17 non-ICU departments, including a psychiatric department across 10 Dutch hospitals. 494 patients, median age 75 (IQR:64-87), 53% male, 46% in ICUs, 29% delirious. DeltaScan recorded 4-minute EEGs, using an algorithm to select the first 96 seconds of artifact-free data for PDA detection. This algorithm was trained and calibrated on two independent datasets. Initial validation of the algorithm for AE involved comparing its output with an expert EEG panel's visual inspection. The primary objective was to assess DeltaScan's accuracy in identifying delirium against a delirium expert panel's consensus. DeltaScan had a 99% success rate, rejecting 6 of the 494 EEG's due to artifacts. Performance showed and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.86 (95% CI: 0.83-0.90) for AE (sensitivity: 0.75, 95%CI=0.68-0.81, specificity: 0.87 95%CI=0.83-0.91. The AUC was 0.71 for delirium (95%CI=0.66-0.75, sensitivity: 0.61 95%CI=0.52-0.69, specificity: 72, 95%CI=0.67-0.77). Our validation aim was an NPV for delirium above 0.80 which proved to be 0.82 (95%CI: 0.77-0.86). Among 84 non-delirious psychiatric patients, DeltaScan differentiated delirium from other disorders with a 94% (95%CI: 87-98%) specificity. DeltaScan can diagnose AE at bedside and shows a clear relationship with clinical delirium. Further research is required to explore its role in predicting delirium-related outcomes. [ABSTRACT FROM AUTHOR]

The Paris System (TPS) provides a uniform reporting system of urine cytology based on well-defined cytologic criteria. Due to their rarity, there are limited data on the utility of TPS in upper urinary tract (UUT) lesions and follow-up histology of cases with abnormal cytology. We aimed to evaluate the utility of TPS for UUT lesions by correlating the cytologic diagnoses using TPS criteria with subsequent histology. Additionally, the diagnostic utility of UroVysion (Abbott) fluorescence in situ hybridization (FISH) was assessed. A total of 148 UUT cytology specimens were retrospectively identified (2018-2022). Cytologic interpretation was performed using TPS, and then correlated with the findings of concurrent or subsequent histologic specimens. The performance of UroVysion FISH was analyzed. Sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting high-grade urothelial carcinoma (HGUC) were determined. Among 83 patients who had concurrent or subsequent histologic specimens, cyto-histologic discrepancy was seen in 7 cases (8.4%). The sensitivity, specificity, PPV, and NPV using TPS criteria for detecting HGUC were 87%, and 92%, 96.4%, and 73%, respectively. UroVysion FISH was performed in 21 patients with atypical cytologic findings. The sensitivity and specificity of UroVysion for detecting HGUC was 75% and 86%, respectively, while PPV and NPV were 86% and 75%, respectively. In our experience, the application of TPS criteria for reporting upper urinary cytology was reliable at detecting UUT lesions, especially HGUC. UroVysion FISH was a valuable ancillary test for detecting HGUC of UUT. • The Paris System (TPS) for reporting urinary cytology is a standardized, evidence-based reporting system and particularly focuses on the detection of high grade urothelial carcinoma. However, limited studies on the utility of TPS in upper urinary tract (UUT) lesions and follow-up histology of cases with abnormal cytology are available. • In this 5-year retrospective study, we described our experience of upper urinary tract cytology specimens with cytologic interpretation using TPS, and further correlated with histology findings and UroVysion FISH test. • A total of 83 patients had concurrent or subsequent histologic specimens and cyto-histologic discrepancy was seen in 9 cases (10.8%). The sensitivity and specificity using TPS criteria for detecting HGUC were 82% and 92%, respectively. • UroVysion FISH was performed in 21 patients with atypical cytologic findings. The sensitivity and specificity of UroVysion for detecting HGUC of UUT was 75% and 86%, respectively. [ABSTRACT FROM AUTHOR]

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P = 0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE] = 0.33 [0.13], P = 0.01 for miR-19a-3p; β[SE] = 0.3 [0.12], P = 0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction = 0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction = 0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995. [ABSTRACT FROM AUTHOR]

Pre-eclampsia with severe features (severe PreE) is associated with heart dysfunction, yet the impact beyond pregnancy, including its association with cardiomyopathic genetic polymorphisms, remains poorly understood. We aimed to characterize the temporal impact of severe PreE on heart function through the 4th trimester in women with and without deleterious cardiomyopathic genetic variants. Pregnant women were enrolled to undergo transthoracic echocardiography (TTE) in late pregnancy and 3 months postpartum. In women with severe PreE a targeted approach to identify pathogenic cardiomyopathic genetic polymorphisms was undertaken, and heart function was compared in carriers and noncarriers. Pregnant women (32 ± 4 years old, severe PreE = 14, control = 8) were enrolled between 2019 - 2021. Women with severe PreE displayed attenuated myocardial relaxation (mitral e' = 11.0 ± 2.2 vs 13.2 ± 2.3 cm/sec, P <.05) in late pregnancy, and on in-silico analysis, deleterious cardiomyopathic variants were found in 58%. At 103 ± 33 days postpartum, control women showed stability in myocardial relaxation (Mitral e' Entry: 13.2 ± 2.3 vs Postpartum: 13.9 ± 1.7cm/sec, P =.464), and genetic negative severe PreE women (G−) demonstrated recovery of diastolic function to control level (Mitral e' Entry: 11.0 ± 3.0 vs Postpartum 13.7 ± 2.8cm/sec, P <.001), unlike their genetic positive (G+) counterparts (Mitral e' Entry: 10.5 ± 1.7 vs Postpartum 10.8 ± 2.4cm/sec, P =.853). Postpartum recovery of heart function after severe PreE is attenuated in women with deleterious cardiomyopathic genetic polymorphisms. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to assess the perspectives of youth survivors of sex trafficking on healthcare to improve care for this vulnerable and often unrecognized population. Semi-structured focus groups were conducted with eight survivors in Southern California who interacted with the healthcare system while being sex trafficked. Interviews were audio- and/or video-recorded and transcribed verbatim. The analysis utilized a grounded theory approach, where researchers reviewed the data collected, then inductively generated codes and themes based on the findings from the interviews. The focus group interviews revealed the following themes: unequal treatment, barriers to patient care, risk identifiers, support, and survivor recommendations. Youth survivors seeking healthcare reported multiple barriers based on their interaction with healthcare providers, such as the lack of provider awareness, education, training, feelings of shame, judgment, fear, racial biases, and lack of empathy. Improving patient outcomes relies on understanding the complexities of human trafficking and implementing an approach to decrease barriers to care. This study resulted in invaluable survivor recommendations with practical solutions on addressing human trafficking and exploitation in the healthcare system. The solutions proposed by participants included strengthening relationships and experiences with healthcare providers by increasing awareness, establishing rapport, creating a safe space, asking questions about their safety and situation, using a non-judgmental approach, and providing resources. • Youth survivors reported multiple barriers to healthcare. • Accurate education and training are essential to identification and response. • Survivors recommended a non-judgmental approach and assurance of safety. • Survivors emphasized the need for more questioning about their experiences. • Access to mental health resources is needed both during and after exploitation. [ABSTRACT FROM AUTHOR]

Managing pregnant individuals with acute respiratory disease secondary to COVID-19 has been a challenge. Most professional societies including the Society for Maternal-Fetal Medicine recommend keeping O2 saturation at ≥95% in pregnant individuals. Reaching this target has been increasingly difficult in some patients, especially during the latest wave of infections attributed to the delta variant of SARS-CoV-2. In the absence of adequate supporting data, and in the setting of a reassuring fetal status, we propose that maternal O2 saturation should be maintained between 92% and 96% for admitted patients with acute respiratory failure who require supplemental O2. This may prevent unnecessary invasive interventions that might not hold maternal or fetal benefit, specifically at very preterm gestational ages. [ABSTRACT FROM AUTHOR]

Background: LDA triggers biosynthesis of endogenous anti-inflammatory molecules, aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4), which may counteract inflammatory process of preeclampsia (PE), and play role in LDA's mechanism of action in PE prevention in high-risk patients.Objective: Investigate the effects of daily LDA on levels of 15-epi-LXA4 in pregnancies at high-risk for developing PE.Materials and Methods: Secondary analysis of multi-centered randomized controlled trial investigating effects of daily LDA (60 mg) in high-risk pregnancies. Maternal samples were drawn at three points: before LDA initiation (13-26 weeks' gestation), 24-28 weeks' gestation (at least two weeks after LDA) and 34-36 weeks' gestation. 15-epi-LXA4 levels were measured by ELISA.Results: Analysis included 82 patients: 63 receiving daily LDA and 29 receiving daily placebo starting between 13 and 25 weeks gestation. Prior to randomization, baseline 15-epi-LXA4 levels were similar between both groups (75.9 pg/mL [IQR; 63.8-114.0] vs 136.2 pg/mL [52.4-476.2]; p = 0.10). Patients receiving daily LDA were noted to have significantly increased levels of 15-epi-LXA4 after LDA administration (136.2 pg/mL [IQR; 52.4-476.2] vs 1758.2 pg/mL [905.4-6638.5]; p < 0.001). They also had higher 15-epi-LXA4 levels compared to those receiving placebo at 24-28 weeks' (50.3 [38.1-94.2] vs 1758.2 [905.4-6638.5]; p < 0.001 and 34-38 weeks' gestation (57.9 [41.9-76.7] vs 2310.3 pg/mL [656.9-10609.4]; p < 0.001). After LDA administration in the second trimester, patients who developed PE had decrease in 15-epi-LXA4 levels compared to those without PE (942 pg/mL [348.3-1810.3] vs 1758.2 pg/mL [905.4-6638.5]; p = 0.129).Conclusion: Daily LDA administration increases 15-epi-LXA4 levels in high-risk pregnancies for PE. In LDA group, pregnancies complicated by PE have lower levels of 15-epi-LXA4 compared to pregnancies without PE. [ABSTRACT FROM AUTHOR]

The role of fatty acid ethyl esters (FAEEs) during human alcoholic pancreatitis is unknown. We compared FAEEs levels with their nonesterified fatty acids (NEFAs) precursors during alcohol intoxication and clinical alcoholic pancreatitis. The pathophysiology underlying FAEEs increase and their role as diagnostic biomarkers for alcoholic pancreatitis was investigated. A prospective blinded study compared FAEEs, NEFAs, and ethanol blood levels on hospitalization for alcoholic pancreatitis (n = 31), alcohol intoxication (n = 25), and in normal controls (n = 43). Serum FAEEs were measured at admission for nonalcoholic pancreatitis (n = 75). Mechanistic cell and animal studies were done. Median FAEEs were similarly elevated during alcohol intoxication (205 nmol/L; 95% confidence interval [CI], 71.8-515 nmol/L, P <.001) and alcoholic pancreatitis (103.1 nmol/L; 95% CI, 53-689 nmol/L, P <.001) vs controls (1.7 nmol/L; 95% CI, 0.02-4.3 nmol/L) or nonalcoholic pancreatitis (8 nmol/L; 95% CI, 1.1-11.5 nmol/L). Alcoholic pancreatitis increased serum NEFAs (1024 ± 710 μmol/L vs 307 ± 185 μmol/L in controls, P <.05). FAEEs comprised 0.1% to 2% of the parent NEFA concentrations. FAEES correlated strongly with NEFAs independent of ethanol levels in alcoholic pancreatitis but not during alcohol intoxication. On receiver operating characteristic curve analysis for diagnosing alcoholic pancreatitis, the area under the curve for serum FAEEs was 0.87 (95% CI, 0.78-0.95, P <.001). In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE with a sustained increase up to 24 hours after intraperitoneal oleic acid plus ethanol administration. The sustained, alcohol-independent, large (20- to 50-fold) increase in circulating FAEEs during alcoholic pancreatitis results from their visceral release and mirrors the 2- to 4-fold increase in parent NEFA. The large areas under the curve of FAEEs on receiver operating characteristic curve analysis supports their role as alcoholic pancreatitis biomarkers. [Display omitted] Fatty acid ethyl esters are biomarkers that can help diagnose alcoholic pancreatitis. They are released by the breakdown of fat during pancreatitis and parallel the parent fatty acids released during fat breakdown. [ABSTRACT FROM AUTHOR]

Large lakes have an impact on regional weather. In addition, they can be both sensitive to and influence regional climate changes. In the climate models that are used to investigate future climate changes, lakes are greatly simplified and sometimes absent. At the regional scale, this can have strong implications for the quality of the model information about the future. Through our work with climate information users in the Laurentian Great Lakes region, we have found that basic credibility of the information requires the underlying climate models simulate lake-atmosphere-land interactions. We are not aware of efforts within the scientific community to make known how individual large lakes are represented in models and how those representations translate to the quality of the data for particular regions. We share our framework for identifying how the Laurentian Great Lakes are represented in the Coupled Model Intercomparison Project (CMIP) version 5 climate models. We found that most CMIP5 models do not simulate the Great Lakes in a way that captures their impact on the regional climate, which is a credibility issue for their projections. We provide a perspective on the usability of CMIP5 for practitioners in the Great Lakes region and offer recommendations for alternative options. [ABSTRACT FROM AUTHOR]

The free-flowing Allier River in central France provides an ideal study system to analyze the colonization and succession of riparian woodlands dominated by the European black poplar (Populus nigra). As displayed in the foreground, dynamic alluvial processes along the meandering river provide extensive gravel bars suitable for seedling colonization, generative or sexual reproduction. Mature woodlands occur along the opposite bank and in those zones, vegetative, clonal or asexual reproduction occurs. Through field measurements, DNA genotyping, dendrochronology, and the extensive interpretations of aerial photographs, the spatiotemporal patterns of generative and vegetative poplar reproduction were analyzed for this study region. This knowledge will benefit the conservation and restoration of the biodiverse but threatened floodplain forests in Europe and elsewhere. • Reproductive ecology of riparian poplars was investigated along a free-flowing river. • Sapling excavation, stand uniformity and genotyping enabled assessments of clonality. • Colonization of barren sites involved generative (sexual, seedlings) reproduction. • Subsequently, vegetative (asexual, clonal) reproduction expanded and infilled stands. • The two reproductive strategies contributed to the woodland diversity and succession. The European black poplar (Populus nigra L.) is a riparian tree that dominates the early successional stages of alluvial floodplain forests throughout Continental Europe. River management and hybrid poplar plantations have contributed to the loss of this foundational species, and measures to conserve and restore the ecologically rich and diverse natural woodlands must sustain poplar reproduction. P. nigra is able to reproduce through either generative (sexual) or vegetative (asexual or clonal) processes and this enhances its chances for preservation in future forests. This research was undertaken to quantify the dominant reproductive strategy of natural black poplar stands, and to determine how this influenced woodland structure and successional processes within the floodplains along the lower Allier River. Two approaches were integrated: (1) analyses of the degree of clonality of stands based on DNA genotyping, sapling excavations, and the uniformity of poplar height and spatial distributions; and (2) retrospective analyses of successional processes to investigate spatiotemporal correspondences with the reproductive strategies. Structural stand patterns indicated the dominant reproductive strategy, with vertical heterogenity indicating clonality, while generative stands were more uniform. One half (50.2%, or 164 ha) of the floodplain study area supported woodlands with P. nigra stands or individuals. Of this area, 42% had apparently reproduced generatively with limited clonality; 43% had dominantly vegetative regeneration with high clonality; and 15% included generatively established, solitary old trees. The generatively and vegetatively reproduced stands displayed generally similar establishment rates but differed in their spatial patterns, with generative seedling bands or patches largely limited to barren streamside sites, while vegetative stands were more diversely distributed. The reproductive types also differed in successional dynamics, with generative stands providing more persistent successional phases with longer residence times. Thus, sexual reproduction enables woodland colonization and introduces genetic diversity, while clonal reproduction expands the population and structural diversity. Both reproductive strategies should be encouraged to provide healthy, diverse and resilient riparian woodlands. [ABSTRACT FROM AUTHOR]

Narrowleaf cottonwoods (Populus angustifolia) occur in disjunct populations along rivers in a north-south corridor of the Rocky Mountain regions from Alberta, Canada, to Arizona, USA. This distribution should allow genetic divergence to provide localized ecophysiological adaptation. To test this, we compared 167 genotypes in ten source populations from across the full latitudinal range of 16° (1800 km). Replicated clonal saplings were grown for three years in a common garden at the northern range limit, where we found that shoot characteristics were correlated with the latitude of origin. Southern populations displayed increased height and stem diameter (populations: r 2 = 0.489 and 0.472) due to extended in-leaf growing seasons. However, this produced a phenological mismatch, with increased fall frost injury and shoot die-back. With increasing latitude of origin there were foliar differences across the populations, with higher chlorophyll content (chl , r 2 = 0.836), nitrogen (N, r 2 = 0.429), and leaf mass per area (LMA, r 2 = 0.474). Similar latitudinal correspondences were observed across the individual genotypes, again with the strongest correlation for chl (r 2 = 0.188). Across the genotypes, chl was positively correlated with leaf length, width, area, and mass, and especially with foliar N (r 2 = 0.354), which was also correlated with foliar δ13C (r 2 = 0.230). The heritable correspondences between source latitude and foliar characteristics could enable vigorous photosynthesis during the shorter, northern growing season, providing latitudinal compensation. Conversely, slower photosynthesis would reduce the foliar aging rate, enabling leaf function through the longer, southern growing season. The alternate foliar strategies could accommodate the limited 'leafspan', or leaf lifespan. This adaptive variation in foliar physiology would impact natural or assisted northward migration of cottonwood populations in response to climate change. It could also be useful for poplar breeding, with northern genotypes contributing genes to increase photosynthetic capacity. Finally, groupings of the populations based on the combined ecophysiological traits were very consistent with genetically defined ecotypes, supporting the evolution of subspecies types within this obligate riparian tree. • Narrowleaf cottonwoods from the full latitudinal range were grown outdoors at the northern limit. • Southern trees displayed longer growth seasons that increased shoot growth, and fall frost injury. • Northern trees displayed increased foliar chlorophyll, nitrogen, and leaf mass per area. • Greener leaves would increase photosynthesis, compensating for the shorter growth season. • Population groupings based on foliar physiology matched genetically characterized ecotypes. [ABSTRACT FROM AUTHOR]

• Non-invasive monitoring of systemic vascular resistance can be a valuable tool to individualize the duration of postpartum magnesium sulfate for preeclampsia with severe features. • 28.6 % of individuals in intervention group had their magnesium sulfate discontinued prior to 24 h with no apparent increase in adverse maternal outcomes. • Our study is one of the first randomized controlled trials using a clinical parameter (systemic vascular resistance) to guide the duration of postpartum magnesium sulfate treatment in individuals with preeclampsia with severe features. To determine the utility of using total peripheral systemic vascular resistance assessed using non-invasive cardiac monitor for individualizing the duration of postpartum magnesium sulfate in individuals with preeclampsia with severe features. Single center pilot randomized controlled trial in which singleton pregnant individuals with preeclampsia with severe features were randomized to 24 h of postpartum magnesium sulfate per standard of care (control group) or individualized duration of postpartum magnesium sulfate based on reduction in post-delivery systemic vascular resistance (intervention group). Systemic vascular resistance was assessed with non-invasive cardiac monitoring using the Cheetah® system. A 30 % reduction (maintained for 1 h) from baseline post-delivery systemic vascular resistance was used as a cutoff for discontinuation of postpartum magnesium sulfate. Our primary outcome was duration of postpartum magnesium sulfate use in hours. Secondary outcomes included a composite of maternal morbidities associated with preeclampsia. Of 53 individuals enrolled, we excluded 6 from this analysis due to insufficient data to assess primary outcome. Baseline characteristics of the control (n = 26) and intervention (n = 21) groups were similar. Six (28.6 %) individuals in intervention group met the systemic vascular resistance criteria and had their postpartum magnesium sulfate discontinued before 24 h. The duration of postpartum magnesium sulfate infusion was shorter in the intervention group (21.6 ± 4.7 h; range: 7–24 h) compared with control group (24 h, p = 0.02). There was no difference in secondary outcomes between the two groups. There was no difference in adverse outcomes in individuals that had magnesium discontinued earlier than 24 h. Non-invasive monitoring of systemic vascular resistance can be a valuable tool to individualize the duration of postpartum magnesium sulfate for preeclampsia with severe features. These findings should be conformed in a larger trial. [ABSTRACT FROM AUTHOR]

There is a growing need for a more accurate, real-time assessment of tumor status and the probability of metastasis, relapse, or response to treatment. Conventional means of assessment include imaging and tissue biopsies that can be highly invasive, may not provide complete information of the disease's heterogeneity, and not ideal for repeat analysis. Therefore, a less-invasive means of acquiring similar information at greater time points is necessary. Liquid biopsies are samples of a patients' peripheral blood and hold potential of addressing these criteria. Ongoing research has revealed that a tumor can release circulating cells, genetic materials (DNA or RNA), and exosomes into circulation. These potential biomarkers can be captured in a liquid biopsy and analyzed to determine disease status. To achieve these goals, numerous technologies have been developed. In this review, we discuss both prominent and newly developed technologies for circulating tumor cell capture and analysis and their clinical impact. [ABSTRACT FROM AUTHOR]

Highlights • Land use related to Dutch consumption was calculated in detail for the years 1990, 1995, 2000, 2005, 2010 and 2013. • Land use decreased during the 1990–2013 period due to increasing agricultural yields, despite growth in GDP and population. • Yields from import regions were used and global average yields; total land use amounted to 0.51 ha per capita using regional yields. • Most land use takes place abroad, mainly in the EU. • Wood, paper and animal products are the most important products. Abstract Effects of Dutch consumption reach far beyond the country borders. The international consequences of consumption are related to imports of many commodities for consumptive needs. The goal of this study was to show the amount and distribution of land needed for Dutch national consumption, inside and outside the national borders. While this question has been investigated in general terms, the present study is motivated by the need to provide more accurate and precise product-level results that can be used in a practical way, for example to guide circular economy policy goals. A model was developed to determine land use of 40 commodities, combining use- /supply-based consumption data with agricultural/forestry yields in the main regions of origin, plus land used for housing, recreation etc. The model thus calculates a land footprint that reflects actual occupied hectares. The model comprises the time series from 1990 to 2013. The land used for the consumptive needs of Dutch people amounts to 8.6 million hectares in 2013, corresponding to 0.51 ha per capita. This is over two and a half times the land area of the Netherlands itself. Land use is primarily related to forestry and agriculture, with paper and meat as important land requiring products. During the 1990–2013 period total land use has decreased by 10%, despite a population increase of 13% and an increase in GDP by 54%. The main causes for this decrease are increased agricultural yields and a decrease in paper and wood consumption after 2010. For the years 1990 and 2013 a comparison was made between land use with actual region-specific yields and global average yields. This exercise showed that, for the year 2013, land use calculated using global average yields was almost twice as much as that calculated using regional yields. This means our commodities originate from regions with relatively productive lands. For the year 1990 the difference was even larger, indicating a converging trend in global yields. In 2013 most land for Dutch consumption was occupied within the EU (53%, of which 20% in the Netherlands) and South America (18%). [ABSTRACT FROM AUTHOR]

Summary Background & aims Indirect comparisons suggest that alternate-day fasting (ADF) may produce greater improvements in body composition, fat distribution, and/or the adipokine profile compared to daily calorie restriction (CR), but this has not been tested directly. In a pre-planned secondary analysis of a randomized controlled trial, we compared changes in the VAT:SAT ratio, FFM:total mass ratio, and the adipokine profile between ADF and CR. Methods Overweight and obese participants (n = 100) were randomized to 1) ADF (alternating every 24-h between consuming 25% or 125% of energy needs); 2) CR (consuming 75% of needs every day); or 3) control (consuming 100% of needs every day) for 24 wk. Results The VAT:SAT ratio did not change in any group. The FFM:total mass ratio increased in both ADF (0.03 ± 0.00) and CR (0.03 ± 0.01) compared to the control group (P < 0.01), with no differences between the intervention groups. Circulating leptin decreased in both the ADF group (−18 ± 6%) and CR group (−31 ± 10%) relative to the control group (P < 0.05), with no differences between the intervention groups. Circulating levels of adiponectin, resistin, IL-6, and TNF-α did not change in either intervention group relative to the control group. Conclusion ADF and CR similarly improve the FFM:total mass ratio and reduce leptin after a 24-wk intervention. Trial registration Clinicaltrials.gov , number NCT00960505. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Cottonwoods, riparian poplars, are facultative phreatophytes and can obtain water from shallow soil moisture originating from rainfall, or from the deeper capillary fringe above the alluvial water table that is recharged by river water infiltration. The correspondence between cottonwood growth and river flows should reveal the dependency upon alluvial groundwater and subsequently, the vulnerability to reduced river flows. To explore this association, we analyzed historic growth patterns of plains cottonwoods (Populus deltoides) along the Red Deer River (RDR), which is at the northwestern limit of the North American Great Plains. We developed chronologies of yearly radial increments (RI) and basal area increments (BAI) and explored correspondences with the environmental records from the past century. In this semi-arid region, the RI or BAI were not correlated with local precipitation while negative correlation with growth season temperature (T) (r = −0.37, p < 0.01) could reflect reduced growth with hot summers. There was correlation between growth and annual river discharge (Q , and particularly log Q that approximates river stage) and this increased with two year averaging (r = 0.51, p < 0.01), reflecting carry-over in the watershed hydrology and in the ecophysiological response. There was correspondence with the Pacific Decadal Oscillation index (PDO, r = −0.45, p < 0.01), which provides multi-decade transitions that influence Rocky Mountain headwater precipitation and other weather characteristics, and river flows. The combination of Q , PDO and T provided the strongest multiple regression model, accounting for 44% of the historic growth variation (52% correspondence for 1953–2013). The RDR was dammed in 1983, enabling winter flow augmentation, but summer flows were sustained and cottonwood growth and the streamflow correspondence persisted. This indicates that it is the pattern of dam operation and not damming per se that determines the fate of established riparian cottonwoods downstream. This study revealed that these cottonwoods are phreatophytic and dependent upon alluvial groundwater that is recharged from the river. This provides a research strategy to determine whether riparian woodlands along other regulated rivers are similarly groundwater-dependent and could be vulnerable to river flow reductions from excessive water withdrawal for irrigation or other uses, or with climate change. [ABSTRACT FROM AUTHOR]

Objective Overfeeding is a strategy for evaluating the effects of excess energy intake. In this secondary analysis we tested the possibility that different levels of dietary protein might differentially modify the response of fatty acyl-carnitines to overfeeding. Methods Twenty-three healthy adult men and women were overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15% (NPD) or 25% (HPD) protein. Plasma fatty acyl-carnitines were measured by gas chromatography/mass spectrometry (GC/MS) at baseline and after 8 weeks of overfeeding. Measurements included: body composition by DXA, energy expenditure by ventilated hood and doubly-labeled water, fat cell size from subcutaneous fat biopsies, and fat distribution by CT scan. Results Analysis was done on 5 groups of fatty acyl-carnitines identified by principal components analysis and 6 individual short-chain fatty acyl carnitines. Higher protein intake was associated with significantly lower 8 week levels of medium chain fatty acids and C2, C4-OH and C 6:1, but higher values of C3 and C5:1 acyl-carnitines derived from essential amino acids. In contrast energy and fat intake were only weakly related to changes in fatty acyl-carnitines. A decease or smaller rise in 8 week medium chain acyl-carnitines was associated with an increase in sleeping energy expenditure (P = 0.0004), and fat free mass (P < 0.0001) and a decrease in free fatty acid concentrations (FFA) (P = 0.0067). In contrast changes in short-chain fatty acyl-carnitines were related to changes in resting energy expenditure (P = 0.0026), and fat free mass (P = 0.0007), and C4-OH was positively related to FFA (P = 0006). Conclusion Protein intake was the major factor influencing changes in fatty acyl carnitines during overfeeding with higher values of most acyl-fatty acids on the low protein diet. The association of dietary protein and fat intake may explain the changes in energy expenditure and metabolic variables resulting in the observed patterns of fatty acyl carnitines [ABSTRACT FROM AUTHOR]

Early identification of individuals with Body dysmorphic disorder (BDD) is essential to direct them to appropriate care and to reduce the chance of developing or maintaining comorbid psychiatric disorders (like an eating disorder (ED)). The present study aimed to develop a simple screener, the Body Dysmorphic Disorder Screener for DSM-5 (BDDS-5), to overcome existing screeners' limitations and test its psychometric properties. The BDDS-5 consists of 12 statements with dichotomous answer options. Specific attention is paid to the readability of the screener for those with lower reading skills. Additional eating disorder screening questions (S section) were added to investigate whether these questions are necessary for detecting potential BDD cases. Finally, the factor structure, internal consistency, and validity of the BDDS-5 were examined within populations with a high risk of screening positive for BDD or ED. Principal axis factor analysis showed that two factors accounted for 63.5% of the variance. The factor analysis was based on polychoric correlation. Based on the BDDS-5, 33 persons (14% of N = 235) were screened as likely BDD cases. Nineteen persons were excluded as potential BDD cases based on the eating disorder related question (question D). Based on the S-section, this turned out to be largely correct for the majority, however, in 8% (n = 4) of the cases BDD was probably missed. The convergent validity appeared to be high (r > 0.80) with three other BDD measures. The BDDS-5 is a valid and widely applicable screener for BDD that may help in the early detection of BDD. The BDDS-5 uses simple wording and is thus suitable for people 8 years and older. • The BDDS-5 follows the DSM-5 criteria closely and uses simple wording suitable for people with lower reading skills. • The BDDS-5 is valid without additional eating disorder questions. • The BDDS-5 is a short and simple screener that may help in the early detection of BDD. • The convergent validity can be considered high when compared to existing BDD screeners. [ABSTRACT FROM AUTHOR]

William Framhein & another v Attorney General [of the Cook Islands] was heard by the Judicial Committee of the Privy Council on 17 November 2021, with the judgment released on 28 February 2022. The case concerned a judicial review of three decisions made by the Cook Islands Government in relation to the establishment of its purse seine fishery in 2013, which is subject to international management arrangements made by the Western and Central Pacific Fisheries Commission. The three decisions at issue were the making of the Skipjack Tuna Purse Seine Fishery Plan 2013, the promulgation of the Marine Resources (Purse Seine Fishery) Regulations 2013, and the adoption and signature of the Sustainable Fisheries Partnership Agreement and Implementation Protocol with the European Union. The case was brought by a private citizen and traditional leader, Mr William Framheim, together with a local environmental NGO, Te Ipukarea Society. The Applicants brought the case to the High Court of the Cook Islands in 2017 and, following the Court's dismissal of their claim, appealed to the Court of Appeal in 2018. Both parties appealed elements of the Court of Appeal's decision to the Privy Council, which is the Cook Islands' highest appeal court. Ultimately, the government prevailed on its cross-appeal to the Privy Council, and the Applicants' appeal was dismissed. The case centers on the interaction between customary international law, the international fisheries legal regime, and domestic law (including indigenous customary law). The findings are significant not just for the Cook Islands, but for all Commonwealth countries engaged in fishing that rely on the Privy Council as a final court of appeal. [ABSTRACT FROM AUTHOR]

Prematurity is a devastating disease with high neonatal morbidity and mortality based on gestational age at birth. Genetic and hormonal signals impact directly on the maternal predisposition to preterm birth or sudden onset of myometrial contractility. Candidate gene or genome-wide approaches are beginning to identify potential variants for women at risk for premature delivery or increased responsiveness to hormonal signals including progesterone. However, a majority of these studies have not yielded definitive results to allow for at this stage for development of personalized therapy. [ABSTRACT FROM AUTHOR]

Objectives To quantify differences in active cervical range of motion (aCROM) between patients with neck pain and those without neck pain, in patients with whiplash-associated disorders (WADs) and nontraumatic neck pain, and in patients with acute complaints versus those with chronic complaints. Data Sources Seven bibliographic databases were searched from inception to April 2015. In addition, a manual search was performed. Study Selection Full articles on a numerical comparison of aCROM in patients with neck pain and asymptomatic control persons of similar ages were included. Two reviewers independently selected studies and assessed risk of bias. Data Extraction Two reviewers extracted the data. Pooled mean differences of aCROM were calculated using a random-effects model. Data Synthesis The search yielded 6261 hits; 27 articles (2366 participants, 13 low risk of bias) met the inclusion criteria. The neck pain group showed less aCROM in all movement directions compared with persons without neck pain. Mean differences ranged from −7.04° (95% CI, −9.70° to −4.38°) for right lateral bending (11 studies) to −89.59° (95% CI, −131.67° to −47.51°) for total aCROM (4 studies). Patients with WADs had less aCROM than patients with nontraumatic neck pain. No conclusive differences in aCROM were found between patients with acute and patients with chronic complaints. Conclusions Patients with neck pain have a significantly decreased aCROM compared with persons without neck pain, and patients with WADs have less aCROM than those with nontraumatic neck pain. [ABSTRACT FROM AUTHOR]

• Unintentional drug overdose accounted for 1,586 deaths and 83,969.78 YLL in perinatal women from 2010 to 2019 in the United States. • For the years 2016–2019, YLL due to unintentional overdose was the third leading cause of YLL overall for this population. • Perinatal American Indian/Native American individuals have a disproportionate number of years of life lost when compared to other racial and ethnic groups. • During the last two years of the study, only American Indian/Native American and Black individuals had increased rates of mortality when compared to other races. The United States has one of the highest maternal mortality rates of developing countries, but the contribution of perinatal drug overdose is not known. Communities of color also have higher rates of maternal morbidity and mortality when compared to White communities, however the contribution due to overdose has not yet been examined in this population. To quantify the years of life lost due to unintentional overdose in perinatal individuals from 2010 to 2019 and assess for disparity by race. Study Design : This was a cross-sectional retrospective study with summary-level mortality statistics for the years 2010–2019 obtained from the Centers for Disease Control (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) mortality file. A total of 1,586 individuals of childbearing age (15–44 years) who died during pregnancy or six weeks postpartum (perinatal) from unintentional overdose in the United States from January 1, 2010 to December 31, 2019 were included. Total years of life lost (YLL) was calculated and summated for White, Black, Hispanic, Asian/Pacific Islander, and American Indian/Native Alaska women. Additionally, the top three overall causes of death were also identified for women in this age group for comparison. Unintentional drug overdose accounted for 1,586 deaths and 83,969.78 YLL in perinatal individuals from 2010 to 2019 in the United States. Perinatal American Indian/Native American individuals had a disproportionate amount of YLL when compared to other ethnic groups, with 2.39% of YLL due to overdose, while only making up 0.80% of the population. During the last two years of the study, only American Indian/Native American and Black individuals had increased rates of mortality when compared to other races. During the ten-year study period, when including the top three causes of mortality, unintentional drug overdoses made up 11.98% of the YLL overall and 46.39% of accidents. For the years 2016–2019, YLL due to unintentional overdose was the third leading cause of YLL overall for this population. Unintentional drug overdose is a leading cause of death for perinatal individuals in the United States, claiming nearly 84,000 years of life over a ten-year period. When examining by race, American Indian/Native American women are most disproportionately affected. [ABSTRACT FROM AUTHOR]

Clostridium perfringens is a Gram-positive, anaerobic, spore-forming bacterium that causes human gas gangrene (clostridial myonecrosis) and food poisoning. Early studies showed that virulence was regulated by the VirSR two-component signal transduction system. However, our identification of the RevR orphan response regulator indicated that more than one system was involved in controlling virulence. To further characterize this virulence-associated regulator, gel mobility shift experiments, coupled with DNase I footprinting, were used to identify the RevR DNA binding sequence. Bioinformatics analysis suggested that an orphan sensor histidine kinase, CPE1757 (renamed RevS), was the cognate sensor of RevR. Interaction between RevS and RevR was demonstrated by use of a bacterial two-hybrid system and validated by protein-protein interaction studies using biolayer interferometry. To assess the involvement of RevS in virulence regulation, the revS gene was inactivated by Targetron insertion. When isogenic wild-type, revS and complemented revS strains were tested in a mouse myonecrosis model, the revS mutant was found to be attenuated in virulence, which was similar to the attenuation observed previously with the revR mutant. However, transcriptional analysis of selected RevR-regulated genes in the revS mutant revealed a different pattern of expression to a revR mutant, suggesting that the RevSR system is more complex than originally thought. Taken together, the results have led to the identification and characterization of the two essential parts of a new regulatory network that is involved in the regulation of virulence in C. perfringens . [ABSTRACT FROM AUTHOR]

Introduction: We performed RNA sequencing with the primary goal of discovering key placental villous trophoblast (VT) and decidua basalis (DB) transcripts differentially expressed in intra-amniotic infection (IAI)-induced preterm birth (PTB).Methods: RNA was extracted from 15 paired VT and DB specimens delivered of women with: 1) spontaneous PTB in the setting of amniocentesis-proven IAI and histological chorioamnionitis (n = 5); 2) spontaneous idiopathic PTB (iPTB, n = 5); and 3) physiologic term pregnancy (n = 5). RNA sequencing was performed using the Illumina HiSeq 2500 platform, and a spectrum of computational tools was used for gene prioritization and pathway analyses.Results: In the VT specimens, 128 unique long transcripts and 7 mature microRNAs differed significantly between pregnancies complicated by IAI relative to iPTB (FDR<0.1). The up-regulated transcripts included many characteristic of myeloblast-derived cells, and bioinformatic analyses revealed enrichment for multiple pathways associated with acute inflammation. In an expanded cohort including additional IAI and iPTB specimens, the expression of three proteins (cathepsin S, lysozyme, and hexokinase 3) and two microRNAs (miR-133a and miR-223) was validated using immunohistochemistry and quantitative PCR, respectively. In the DB specimens, only 11 long transcripts and no microRNAs differed significantly between IAI cases and iPTB controls (FDR<0.1). Comparison of the VT and DB specimens in each clinical scenario revealed signatures distinguishing these placental regions.Discussion: IAI is associated with a transcriptional signature consistent with acute inflammation in the villous trophoblast. The present findings illuminate novel signaling pathways involved in IAI, and suggest putative therapeutic targets and potential biomarkers associated with this condition. [ABSTRACT FROM AUTHOR]

Background: Procalcitonin (PCT) is a new biomarker with a higher accuracy in the diagnosis of bacterial infections. Utilization of PCT may reduce the number of unnecessary antibiotics prescribed to patients and consequently may decrease the rise in antibiotic resistance. The aim of this systematic review is to determine if a PCT-guided algorithm can safely reduce the number of antibiotics prescribed to all patients with a suspected of infection in the emergency department (ED).Methods: MEDLINE, EMBASE, Web of Science, COCHRANE central, PubMed publisher, and Google scholar were searched. Two reviewers performed the screening independently. The QUADAS 2 tool was used to assess quality.Results: In total, 1621 articles were screened. Nine articles were included in the analysis. In the 6 studies on adult patients, only patients with respiratory tract infections were investigated. In these studies, a cutoff value of 0.25 μg/L was used, and PCT-guided therapy reduced the number of prescribed antibiotics significantly. Three studies were on pediatric patients, 2 on fever without source and 1 on respiratory complaints. Procalcitonin-guided therapy did not reduce antibiotic prescription in children. Procalcitonin-guided therapy did not result in an increase in adverse events in any of the studies.Discussion: Procalcitonin-guided therapy in the ED is only studied in subpopulations, where it was effective and safe in adult patients with respiratory tract infections and not effective but safe nonetheless in specific pediatric populations. Nonadherence is a significant problem in prospective PCT-guided therapy studies. There is not enough evidence to use PCT-guided therapy in a general ED population. [ABSTRACT FROM AUTHOR]

Optimizing sample preparation for the isotopic measurement of 10 Be extracted from quartz mineral separates has a direct positive effect on the accuracy and precision of isotopic analysis. Here, we demonstrate the value of tracing Be throughout the extraction process (both after dissolution and after processing), producing pure Be (by optimizing ion exchange chromatography methods and quantifying quartz mineral separate and final Be fraction purity), and minimizing backgrounds (through reducing both laboratory process blanks and 10 B isobaric interference). These optimization strategies increase the amount of 10 Be available for analysis during accelerator mass spectrometry (AMS), while simultaneously decreasing interference and contamination, and ensuring that sample performance matches standard performance during analysis. After optimization of our laboratory's extraction methodology, 9 Be 3+ ion beam currents measured during AMS analysis, a metric for sample purity and Be yield through the extraction process, matched the 9 Be 3+ beam currents of AMS standards analyzed at the same time considering nearly 800 samples. Optimization of laboratory procedures leads to purer samples that perform better, more consistently, and more similarly to standards during AMS analysis, allowing for improved precision and accuracy of measurements used for dating and quantification of Earth surface processes. [ABSTRACT FROM AUTHOR]

Abstract Water levels on Lake Ontario, the most downstream of the Laurentian Great Lakes, reached a record high in the spring of 2017. This event was accompanied by widespread flooding and displacement of families. Water levels across all of the Great Lakes have risen over the past several years following a period of record low levels. When levels were low, public and expert discussion focused on the possibility that low levels would continue into the future due to climate change, diversions of water from the lakes, and dredging. During the current high water period, variability is being attributed to water management, despite evidence of unusually high precipitation and river flows across the region. Understanding and communicating the drivers behind water level variability, particularly in light of recent extremes, is a fundamental step towards improving regional water resources management and policy. [ABSTRACT FROM AUTHOR]

Background Courses for migrants in Europe are mostly aimed at literacy in western languages as a means for participation in society. These curricula are not suitable for migrants without previous basic education, which leaves groups of migrants vulnerable to alienation and without support for social integration. Method The IDEAL-programme (Integrating Disadvantaged Ethnicities through Adult Learning), which takes a participatory didactic approach and in which daily personal and family life is the starting point for learning, was provided and evaluated in the Netherlands and Sweden in 2011–2013. The participants ( N = 16) were migrant mothers of Berber and Arabic origin without formal educational experience. The teachers shared the same background and served as role model facilitators and social brokers. Results Through exploring their personal narratives, the participants showed new insights, skills, and attitudes on the topics of communication, health and parenting. All participants showed progress in language acquisition and participation in society. The Dutch group of migrant mothers reported to use less physical punishment and threats to their children, and to practise more positive parenting skills instead. Discussion Literacy oriented programmes for social integration are not suitable for all migrants and do not encourage acculturation. The proposed method offers a feasible alternative, so that migrants may be more adequately supported in their efforts for social integration in receiving societies. In order to advance the future development of participatory programmes for civic education, several key intervention design principles and political conditions are discussed. [ABSTRACT FROM AUTHOR]