Roots selectively decompose litter to mine nitrogen and build new soil carbon.

Plant-microbe interactions in the rhizosphere shape carbon and nitrogen cycling in soil organic matter (SOM). However, there is conflicting evidence on whether these interactions lead to a net loss or increase of SOM. In part, this conflict is driven by uncertainty in how living roots and microbes alter SOM formation or loss in the field. To address these uncertainties, we traced the fate of isotopically labelled litter into SOM using root and fungal ingrowth cores incubated in a Miscanthus x giganteus field. Roots stimulated litter decomposition, but balanced this loss by transferring carbon into aggregate associated SOM. Further, roots selectively mobilized nitrogen from litter without additional carbon release. Overall, our findings suggest that roots mine litter nitrogen and protect soil carbon.

Proteogenomic characterization of difficult-to-treat breast cancer with tumor cells enriched through laser microdissection.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors. METHODS: We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers. RESULTS: We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA-protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors. CONCLUSIONS: This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.

Racial and Ethnic Patterning of Low Birth Weight, Normal Birth Weight, and Macrosomia.

Both low birthweight (<2500 g; LBW) and macrosomia (>4000 g) are considered adverse birth outcomes and are associated with later poor health conditions, yet the social determinants of macrosomia are understudied. In this study, we explore patterning of LBW, normal birthweight, and macrosomia by race/ethnicity and nativity. We examined data from all live births between 1999 and 2014 in New Jersey with a non-missing, plausible value of birthweight (n = 1,609,516). We compared the risk for LBW and macrosomia among non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Asian mothers, and between the US- and native-born. For Hispanics and Asians, we also examined differences by country of origin. The racial/ethnic patterns for macrosomia mirrored those of LBW, suggesting that the factors underlying LBW shift birthweight distributions. For example, non-Hispanic White mothers had the lowest risk for LBW and the highest risk for macrosomia. Nativity patterns differed by subgroup, however, with unique risks for macrosomia among some origin groups, such as foreign-born Cubans. The racial/ethnic and nativity patterns of macrosomia do not completely mirror those of LBW, suggesting some distinct social risk factors for macrosomia. Our findings raise questions about whether and how racial/ethnic and nativity patterning in both low and excess birthweight is retained in later conditions, such as childhood obesity.

An Examination of Preterm Birth and Residential Social Context among Black Immigrant Women in California, 2007-2010.

The foreign-born black population contributes a considerable amount of heterogeneity to the US black population. In 2005, black immigrants accounted for 20% of the US black population. Compared to native-born black women, black immigrant women are at lower risk for adverse birth outcomes, including preterm birth. Some scholars posit that differential exposures to socioeconomic disadvantage and structural racism in the residential context may account for this advantage. However, to date, few studies offer comprehensive examinations of the black immigrant residential social context, particularly in settlement regions beyond predominantly black and historically segregated regions. Further, studies examining the black immigrant residential context typically use a single indicator, which limits discussion of the intersecting domains that simultaneously increase or decrease risk among black immigrants. We addressed these gaps by examining black immigrant neighborhoods in the state of California, where racial residential segregation of the black population is low. We operationalized the residential context of black immigrant women using three distinct attributes: immigrant co-ethnic density, black racial concentration, and neighborhood deprivation. We linked 2007-2010 California birth records of black immigrant women and 2010 census data on tract-level social attributes (N = 6930). OLS regression analyses showed that immigrant co-ethnic density, black racial concentration and neighborhood deprivation were not associated with preterm birth among black immigrants. Our findings indicate that in California, residential social context has little relation to black immigrant preterm birth-a finding that is unique compared to residential settings of other settlement contexts.

Neighborhood affluence protects against antenatal smoking: evidence from a spatial multiple membership model.

A spatial multiple membership model formalizes the effect of neighborhood affluence on antenatal smoking. The data are geocoded New Jersey birth certificate records linked to United States census tract-level data from 1999 to 2007. Neighborhood affluence shows significant spatial autocorrelation and local clustering. Better model fit is observed when incorporating the spatial clustering of neighborhood affluence into multivariate analyses. Relative to the spatial multiple membership model, the multilevel model that ignores spatial clustering produced downwardly biased standard errors; the effective sample size of the key parameter of interest (neighborhood affluence) is also lower. Residents of communities located in high-high affluence clusters likely have better access to health-promoting institutions that regulate antenatal smoking behaviors.

Neighborhood Disadvantage and Neighborhood Affluence: Associations with Breastfeeding Practices in Urban Areas.

Objective To estimate the associations between neighborhood disadvantage and neighborhood affluence with breastfeeding practices at the time of hospital discharge, by race-ethnicity. Methods We geocoded and linked birth certificate data for 111,596 live births in New Jersey in 2006 to census tracts. We constructed indices of neighborhood disadvantage and neighborhood affluence and examined their associations with exclusive (EBF) and any breastfeeding in multilevel models, controlling for individual-level confounders. Results The associations of neighborhood disadvantage and affluence with breastfeeding practices differed by race-ethnicity. The odds of EBF decreased as neighborhood disadvantage increased for all but White women [Asian: Adjusted odds ratio (AOR) 0.82 (95% confidence interval (CI) 0.69-0.97); Black: AOR 0.77 (95% CI 0.70-0.86); Hispanic: AOR 0.78 (95% CI 0.70-0.86); White: AOR 0.99 (95% CI 0.91-1.08)]. The odds of EBF increased as neighborhood affluence increased for Hispanic [AOR 1.19 (95% CI 1.08-1.31)] and White [AOR 1.12 (95% CI 1.06-1.18)] women only. The odds of any breastfeeding decreased with increasing neighborhood disadvantage only for Hispanic women [AOR 0.85 (95% CI 0.79-0.92)], and increased for White women [AOR 1.16 (95% CI 1.07-1.26)]. The odds of any breastfeeding increased as neighborhood affluence increased for all except Hispanic women [Asian: AOR 1.31 (95% CI 1.13-1.51); Black: AOR 1.19 (95% CI 1.07-1.32); Hispanic: AOR 1.08 (95% CI 0.99-1.18); White: AOR 1.30 (95% CI 1.24-1.38)]. Conclusions Race-ethnic differences in associations between neighborhood disadvantage and affluence and breastfeeding practices at the time of hospital discharge indicate the need for specialized support to improve access to services.

A systematic review of primary care models for non-communicable disease interventions in Sub-Saharan Africa.

BACKGROUND: Chronic diseases, primarily cardiovascular disease, respiratory disease, diabetes and cancer, are the leading cause of death and disability worldwide. In sub-Saharan Africa (SSA), where communicable disease prevalence still outweighs that of non-communicable disease (NCDs), rates of NCDs are rapidly rising and evidence for primary healthcare approaches for these emerging NCDs is needed. METHODS: A systematic review and evidence synthesis of primary care approaches for chronic disease in SSA. Quantitative and qualitative primary research studies were included that focused on priority NCDs interventions. The method used was best-fit framework synthesis. RESULTS: Three conceptual models of care for NCDs in low- and middle-income countries were identified and used to develop an a priori framework for the synthesis. The literature search for relevant primary research studies generated 3759 unique citations of which 12 satisfied the inclusion criteria. Eleven studies were quantitative and one used mixed methods. Three higher-level themes of screening, prevention and management of disease were derived. This synthesis permitted the development of a new evidence-based conceptual model of care for priority NCDs in SSA. CONCLUSIONS: For this review there was a near-consensus that passive rather than active case-finding approaches are suitable in resource-poor settings. Modifying risk factors among existing patients through advice on diet and lifestyle was a common element of healthcare approaches. The priorities for disease management in primary care were identified as: availability of essential diagnostic tools and medications at local primary healthcare clinics and the use of standardized protocols for diagnosis, treatment, monitoring and referral to specialist care.

Dignity in long-term care: An application of Nordenfelt's work.

BACKGROUND: The concept of dignity is recognised as a fundamental right in many countries. It is embedded into law, human rights legislation and is often visible in organisations' philosophy of care, particularly in aged care. Yet, many authors describe difficulties in defining dignity and how it can be preserved for people living in long term care. OBJECTIVES: In this article, Nordenfelt's 'four notions of dignity' are considered, drawing on research literature addressing the different perspectives of those who receive, observe or deliver care in the context of the long-term care environment. METHODS: A review of the literature was undertaken using the terms 'nursing homes', 'residential care' or 'long-term care'. The terms were combined and the term 'human dignity' was added. A total of 29 articles met the inclusion criteria from the United Kingdom (14), United States (2), Australia (1), Sweden (3), Hong Kong (2), Norway (3), Nordic (1), Taiwan (1), Netherlands (1). Ethical Considerations: Every effort has been made to ensure an unbiased search of the literature with the intention of an accurate interpretation of findings. DISCUSSION: The four notions of dignity outlined by Nordenfelt provide a comprehensive description of the concept of dignity which can be linked to the experiences of people living in long-term care today and provide a useful means of contextualising the experiences of older people, their families and significant others and also of staff in long-term care facilities. Of particular interest are the similarities of perspectives of dignity between these groups. The preservation of dignity implies that dignity is a quality inherent in us all. This links directly to the exploration and conclusions drawn from the literature review. Conversely, promoting dignity implies that dignity is something that can be influenced by others and external factors. Hence, there are a number of implications for practice. CONCLUSION: We suggest that two of Nordenfelt's notions, 'dignity of identity' and 'dignity of Menschenwüde', are a common thread for residents, family members and staff when conceptualising dignity within long-term care environments.

Mitoxantrone-Induced Cardiotoxicity in Acute Myeloid Leukemia-A Velocity Vector Imaging Analysis.

BACKGROUND: The purpose of this investigation was to: (1) determine incidence and predictors of mitoxantrone-induced early cardiotoxicity and (2) study left ventricular mechanics before and after receiving mitoxantrone. METHOD AND RESULTS: We retrospectively analyzed 80 subjects diagnosed with acute myeloid leukemia (AML) who underwent chemotherapy with bolus high-dose mitoxantrone. Echocardiographic measurements were taken at baseline and at a median interval of 55 days after receiving mitoxantrone. Thirty-five (44%) of the patients developed clinically defined early cardiotoxicity, 29 (36%) of which developed heart failure. There was a significant decrease in the ejection fraction (EF) not only in the cardiotoxicity group (17.6 ± 14.8%, P < 0.001) but also in the noncardiotoxicity group (5.3 ± 8.4%, P < 0.001). Decrease in global longitudinal strain (GLS) (-3.7 ± 4.5, P < 0.001 vs. -2.4 ± 4.3, P = 0.01) and global circumferential strain (GCS) (-5.6 ± 9, P = 0.003 vs. -5.3 ± 8.7, P < 0.001) was significant in both the cardiotoxicity and noncardiotoxicity group, respectively. A multivariate model including baseline left ventricular end-systolic diameter, baseline pre-E/A ratio, and baseline pre-E/e' ratio was found to be the best-fitted model for prediction of mitoxantrone-induced early clinical cardiotoxicity. CONCLUSION: High-dose mitoxantrone therapy is associated with an excellent remission rate but with a significantly increased risk of clinical and subclinical early cardiotoxicity and heart failure. Mitoxantrone-induced systolic dysfunction is evident from reduction in EF, increase in Tei index, and significant reduction in GLS and GCS. Baseline impaired ventricular relaxation evident from higher E/e' ratio and lower E/A ratio independently predicts increased risk of mitoxantrone-induced early cardiotoxicity.

Incidence of Surgical Reintervention for Benign Prostatic Hyperplasia Following Prostatic Urethral Lift, Transurethral Resection of the Prostate, and Photoselective Vaporization of the Prostate: A TriNetX Analysis.

Background: Prostatic urethral lift, or UroLift, has gained popularity as a treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Surgical reintervention rates are a reliable indicator for treatment durability. Objective: The objective of this study was to utilize TriNetX, a third-party database, to investigate the incidence of surgical reintervention following UroLift, transurethral resection of the prostate (TURP), and photoselective vaporization of the prostate (PVP) procedures for BPH from 2015 to 2018. Design setting and participants: Male patients aged 18-100 yr diagnosed with BPH were identified in the TriNetX Diamond Network database between January 2015 and December 2018. Cohorts of individuals undergoing their first UroLift procedure were built using Current Procedural Terminology and International Classification of Diseases 10th Revision codes. TURP and PVP cohorts were built as comparison groups. The cohorts were then queried for subsequent BPH-related procedures. Outcome measurements and statistical analysis: Reprocedure rates were assessed and descriptive statistics were used. Results and limitations: The mean age at first-time UroLift was 70.1 ± 9.4 yr (n = 14 343). Cumulative reprocedure rates collected after first-time UroLift included 1 yr after UroLift (5.1%, n = 14 343) and 4 yr after UroLift (16.1%, n = 710), with an average annual increase of +3.6% per year following 1 yr after the procedure. Comparatively, TURP (n = 22 071) and PVP (n = 14 110) had 4-yr reprocedure rates of 7.5% and 7.8%, respectively, during the same timeframe. Limitations include a lack of clinical data and loss of follow-up data outside the Diamond Network. Conclusions: The reprocedure rate of UroLift at 4 yr is double the rate of TURP and PVP. In appropriately selected patients, UroLift might be a suitable option for those who desire symptomatic relief from BPH with minimal erectile and ejaculatory side effects. However, the risk of secondary surgical intervention should be considered when considering BPH treatments. Patient summary: We compared the reintervention rates of prostatic urethral lift (PUL), transurethral resection of the prostate (TURP), and photoselective vaporization of the prostate (PVP) using the TriNetX database, and have found that the highest reintervention rates were for PUL of 16% at 4 yr of follow-up, compared with about 8% for those who had TURP and PVP. Interestingly, the most common reintervention was the same operation at 1 yr. This has important implications when counseling patients about the durability of these various outlet procedures for BPH.

Basophils Play a Protective Role in the Recovery of Skin Barrier Function from Mechanical Injury in Mice.

Physical trauma disrupts skin barrier function. How the skin barrier recovers is not fully understood. We evaluated in mice the mechanism of skin barrier recovery after mechanical injury inflicted by tape stripping. Tape stripping disrupted skin barrier function as evidenced by increased transepidermal water loss. We show that tape stripping induces IL-1-, IL-23-, and TCRγδ+-dependent upregulation of cutaneous Il17a and Il22 expression. We demonstrate that IL-17A and IL-22 induce epidermal hyperplasia, promote neutrophil recruitment, and delay skin barrier function recovery. Neutrophil depletion improved the recovery of skin barrier function and decreased epidermal hyperplasia. Single-cell RNA sequencing and flow cytometry analysis of skin cells revealed basophil infiltration into tape-stripped skin. Basophil depletion upregulated Il17a expression, increased neutrophil infiltration, and delayed skin barrier recovery. Comparative analysis of genes differentially expressed in tape-stripped skin of basophil-depleted mice and Il17a-/- mice indicated that basophils counteract the effects of IL-17A on the expression of epidermal and lipid metabolism genes important for skin barrier integrity. Our results demonstrate that basophils play a protective role by downregulating Il17a expression after mechanical skin injury, thereby counteracting the adverse effect of IL-17A on skin barrier function recovery, and suggest interventions to accelerate this recovery.

Effect of ASCO/CAP guidelines for determining ER status on molecular subtype.

BACKGROUND: Determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is standard for predicting prognosis and determining treatment options for patients with breast cancer. In 2010, the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) issued guidelines that tumors with ≥1% positively staining cells should be considered ER positive. Here, we determined how this cutoff relates to molecular subtype. METHODS: Clinicopathological characteristics were compared between ER-negative, ER-positive, and low-ER-staining (1-10%) tumors using chi-square analysis with P<0.05 defining statistical significance. Gene expression data were generated for 26 low-ER-staining tumors, and their intrinsic subtype determined. Immunohistochemistry (IHC)-defined surrogate subtypes, using the threshold of positivity defined by ASCO/CAP guidelines, were compared with molecular subtypes. RESULTS: Low-ER-staining tumors were clinicopathologically more similar to ER-negative than to ER-positive tumors; 88% of low-staining tumors were basal like or HER2 enriched. Only those tumors expressing 10% ER-positive cells were classified as luminal A subtype. CONCLUSIONS: Under ASCO/CAP guidelines, tumors with 1-10% ER staining would be classified as ER positive, yet most are basal like or HER2 enriched and have pathological features similar to ER-negative tumors. Clinical trials seeking to treat tumors of ER-negative basal-like and/or HER2-enriched subtypes should thus not preclude enrollment based solely on results of ER immunohistochemistry. As ER status is a critical element in the choice of treatments for patients with breast cancer, it is imperative that the most effective method for classifying tumors be developed.

Fungivorous nematodes drive microbial diversity and carbon cycling in soil.

Soil bacteria and fungi mediate terrestrial biogeochemical cycling, but we know relatively little about how trophic interactions influence their community composition, diversity, and function. Specifically, it is unclear how consumer populations affect the activity of microbial taxa they consume, and therefore the interaction of those taxa with other members of the microbial community. Due to its extreme diversity, studying trophic dynamics in soil is a complex feat. Seeking to address these challenges, we performed a microcosm-based consumer manipulation experiment to determine the impact of a common fungal-feeding nematode (Aphelenchus avenae) on soil microbial community composition, diversity, and activity (e.g., C cycling parameters). Fungivory decreased fungal and bacterial α-diversity and stimulated C and N cycling, possibly via cascading impacts of fungivory on bacterial communities. Our results present experimental evidence that soil trophic dynamics are intimately linked with microbial diversity and function, factors that are key in understanding global patterns in biogeochemical cycling.

Illuminating the daily life experiences of adolescents with and without ADHD: protocol for an ecological momentary assessment study.

INTRODUCTION: Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at elevated risk of a range of difficulties, among which emotion regulation, peer and co-occurring mental health problems are prominent challenges. To better support adolescents with ADHD, ecologically valid interventions that can be embedded in daily life to target the most proximal antecedents of these challenges are needed. Ecological momentary assessment (EMA) designs are ideally suited to meeting this need. METHODS AND ANALYSES: In the mental health in the moment ADHD study, we will use an EMA design to capture the daily life experiences of approximately 120 adolescents aged 11-14 years with a clinical diagnosis of ADHD and the same number of age-matched and gender-matched peers without a diagnosis of ADHD. We will combine this with comprehensive information gathered from online surveys. Analysing the data using techniques such as dynamic structural equation modelling, we will examine, among other research questions, the role of emotion regulation and peer problems in mediating the links between characteristics of ADHD and commonly co-occurring outcomes such as anxiety, depression and conduct problems. The results can help inform interventions to support improved peer functioning and emotion regulation for adolescents with ADHD. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion through the National Health Service ethical review board and the University of Edinburgh PPLS Research Ethics panel. The results will be disseminated through journal publications, conferences and seminar presentations and to relevant stakeholders, such as those with ADHD, their families and clinicians.

Speckle echocardiographic left atrial strain and stiffness index as predictors of maintenance of sinus rhythm after cardioversion for atrial fibrillation: a prospective study.

BACKGROUND: Echocardiographic left atrial (LA) strain parameters have been associated with atrial fibrillation (AF) in prior studies. Our goal was to determine if strain measures [peak systolic longitudinal strain (LAS) and stiffness index (LASt)] changed after cardioversion (CV); and their relation to AF recurrence. METHODS AND RESULTS: 46 participants with persistent AF and 41 age-matched participants with no AF were recruited. LAS and LASt were measured before and immediately after CV using 2D speckle tracking imaging (2DSI). Maintenance of sinus rhythm was assessed over a 6-month follow up. Mean LAS was lower, and mean LASt higher, in participants with AF before CV as compared to control group (11.9±1.0 vs 35.7±1.7, p<0.01 and 1.31±0.17 vs 0.23±0.01, p<0.01, respectively). There was an increase in the mean LAS immediately after CV (11.9±1.0 vs 15.9±1.3, p<0.01), whereas mean LASt did not change significantly after CV (p=0.62). Although neither LAS nor LASt were independently associated with AF recurrence during the follow-up period, change in LAS after cardioversion (post-CV LAS-pre-CV LAS) was significantly higher among individuals who remained in sinus rhythm when compared to individuals with recurrent AF (3.6±1.1 vs 0.4±0.8, p=0.02). CONCLUSIONS: LAS and LASt differed between participants with and without AF, irrespective of the rhythm at the time of echocardiographic assessment. Baseline LAS and LASt were not associated with AF recurrence. However, change in LAS after CV may be a useful predictor of recurrent arrhythmia.

A review of amoebic liver abscess for clinicians in a nonendemic setting.

Amoebic liver abscess (ALA) is an uncommon but potentially life-threatening complication of infection with the protozoan parasite Entamoeba histolytica. E histolytica is widely distributed throughout the tropics and subtropics, causing up to 40 million infections annually. The parasite is transmitted via the fecal-oral route, and once it establishes itself in the colon, it has the propensity to invade the mucosa, leading to ulceration and colitis, and to disseminate to distant extraintestinal sites, the most common of which is the liver. The authors provide a topical review of ALA and summarize clinical data from a series of 29 patients with ALA presenting to seven hospitals in Toronto, Ontario, a nonendemic setting, over 30 years.

The effect of prescribing antibiotics with opioids on the development of opioid use disorder: a national database study.

The goal of this study was to examine the impact of inpatient- or emergency department- prescribed antibiotic treatment in combination with opioids on the risk of developing opioid use disorder 12 months following discharge from the hospital. The authors conducted a propensity score-matched cohort study with data from the TriNetX Research Network database to identify adult subjects (18-65 years old) with no previous history of an opioid use disorder. Three cohorts were defined for the analyses: subjects who were prescribed an opioid, opioid in combination with an antibiotic, or an antibiotic while in the emergency department or inpatient unit, from the years 2012 to 2018. The diagnosis of an Opioid Related Disorder (F11.10-F11.20) 12 months following discharge from the emergency department or inpatient unit was then observed within the cohorts following the index event as identified by the ICD-10 procedural coding system. Primary analysis (propensity-score matched on age and sex) showed that opioids prescribed in combination with antibiotics had a protective effect against the development of opioid use disorder. This effect was consistent throughout all of the years included in this study with the smallest protective effect observed in 2018 (2012 risk ratio = 1.27 (95% CI: 1.23, 1.32); 2018 risk ratio: 1.03 (95% CI: 1.01, 1.05). These findings suggest that opioids prescribed in combination with antibiotics in the hospital setting are protective against the development of OUD at later time points following hospital discharge.

Acute effects of vasoactive medications in patients with parallel circulation awaiting hybrid or Norwood procedure.

Background: Vasoactive medications are frequently used in the preoperative stage to balance the pulmonary and systemic blood flow. However, not much is known about the effects of these agents during this stage. Aims: The primary objective of this study was to characterize the acute effects of vasoactive medications in children with parallel circulation before either the hybrid or Norwood procedure. Setting and Designs: This is a single-center, cross-sectional, retrospective study. Methods: Hemodynamic and systemic oxygen delivery data were captured from patients' vital signs, arterial blood gases, near-infrared spectroscopy monitoring (NIRS). Data for each patient were collected before the initiation of a vasoactive medication and again 6 h after. Statistical Analysis: Data were analyzed using paired t-tests, and analysis of covariance. Results: A total of 139 patients were identified. After data extraction the following patients were included before the initial intervention: 7 were on milrinone, 22 were on dopamine, and 17 were on dobutamine. Dopamine and dobutamine were found to significantly increase systolic blood pressure. Only dopamine increased pH (mean difference 0.04), decreased paCO2 (mean difference -7.1), decreased lactate (mean difference -0.6 mmol/L), and decreased in bedside Qp: Qs (mean difference -7.5) after continuous infusion for 6 h. Milrinone was not associated with any significant hemodynamic change. Conclusion: In this study, dopamine was independently associated with improvement in markers of systemic oxygen delivery 6 h after initiation. Dobutamine and dopamine were associated with increased in blood pressure. Well-powered studies are required to detect changes in lactate and NIRS.

Assessing the quality of RNA isolated from human breast tissue after ambient room temperature exposure.

High quality human tissue is essential for molecular research, but pre-analytical conditions encountered during tissue collection could degrade tissue RNA. We evaluated how prolonged exposure of non-diseased breast tissue to ambient room temperature (22±1°C) impacted RNA quality. Breast tissue received between 70 to 190 minutes after excision was immediately flash frozen (FF) or embedded in Optimal Cutting Temperature (OCT) compound upon receipt (T0). Additional breast tissue pieces were further exposed to increments of 60 (T1 = T0+60 mins), 120 (T2 = T0+120 mins) and 180 (T3 = T0+180 mins) minutes of ambient room temperature before processing into FF and OCT. Total exposure, T3 (T0+180 mins) ranged from 250 minutes to 370 minutes. All samples (FF and OCT) were stored at -80°C before RNA isolation. The RNA quality assessment based on RNA Integrity Number (RIN) showed RINs for both FF and OCT samples were within the generally acceptable range (mean 7.88±0.90 to 8.52±0.66). No significant difference was observed when RIN at T0 was compared to RIN at T1, T2 and T3 (FF samples, p = 0.43, 0.56, 0.44; OCT samples, p = 0.25, 0.82, 1.0), or when RIN was compared between T1, T2 and T3. RNA quality assessed by quantitative real-time PCR (qRT-PCR) analysis of beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin A (CYPA), and porphobilinogen deaminase (PBGD) transcripts showed threshold values (Ct) that indicate abundant and intact target nucleic acid in all samples (mean ranging from 14.1 to 25.3). The study shows that higher RIN values were obtained for non-diseased breast tissue up to 190 minutes after resection and prior to stabilization. Further experimental exposure up to 180 minutes had no significant effect on RIN values. This study strengthens the rationale for assessing RIN and specific gene transcript levels as an objective method for determining how suitable RNA will be for a specific research purpose ("fit-for purpose").