Correlating Severity of Pulmonary Hypertension by Echocardiogram with Mortality in Premature Infants with Bronchopulmonary Dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth. Infants with BPD are at increased risk for pulmonary hypertension (PH). Cardiac catheterization is the gold standard for diagnosing PH, but cardiac catheterization is challenging to perform in small, sick, premature infants. The utility of echocardiography for diagnosing PH and predicting outcomes in extremely premature infants has not been clearly defined. Therefore, we sought to use predefined criteria to diagnose PH by echocardiogram and relate PH severity to mortality in extremely premature infants with BPD. STUDY DESIGN: Echocardiograms from 46 infants born ≤28 weeks' postmenstrual age with a diagnosis of BPD were assessed for PH by three pediatric cardiologists using predefined criteria, and survival times among categories of PH patients were compared. A total of 458 echocardiograms were reviewed, and 15 (33%) patients were found to have at least moderate PH. Patients with at least moderate PH had similar demographic characteristics to those with no/mild PH. RESULTS: Ninety percent of infants without moderate to severe PH survived to hospital discharge, compared with 67% of infants with at least moderate PH (p = 0.048). Patients with severe PH had decreased survival to hospital discharge (38%) compared with moderate (100%) and no/mild PH (90%) groups. Kaplan-Meier survival curves also differed among PH severity groups (Wilcoxon p < 0.001). CONCLUSION: Using predefined criteria for PH, premature infants with BPD can be stratified into PH severity categories. Patients diagnosed with severe PH by echocardiogram have significantly reduced survival. KEY POINTS: · A composite score definition of PH by echocardiogram showed high inter- and intrarater reliability.. · Infants with severe PH by echocardiogram had decreased survival rates.. · Early diagnosis of PH by echocardiogram dictates treatment which may improve outcomes..

Single cell RNA sequencing reveals immunomodulatory mechanism of stem cell factor and granulocyte colony-stimulating factor treatment in the brains of aged APP/PS1 mice.

Alzheimer's disease (AD) leads to progressive neurodegeneration and dementia. AD primarily affects older adults with neuropathological changes including amyloid-beta (Aß) deposition, neuroinflammation, and neurodegeneration. We have previously demonstrated that systemic treatment with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF), reduces Aß load, increases Aß uptake by activated microglia and monocytes/macrophages (Mo/Mac), reduces neuroinflammation, and restores dendrites and synapses in the brains of aged APPswe/PS1dE9 (APP/PS1) mice. However, the mechanisms underlying SCF+G-CSF-enhanced brain repair in aged APP/PS1 mice remain unclear. This study used a transcriptomic approach to explore the mechanisms by which SCF+G-CSF treatment alters the functions of microglia and Mo/Mac in the brains of 28-month-old APP/PS1 mice. After 5-day injections of SCF+G-CSF, single-cell RNA sequencing was performed on CD11b + microglia and Mo/Mac isolated from the brain. Flow cytometry was used for identifying CD11b + microglia and Mo/Mac in the brain. Both transcriptional profiling and flow cytometry data demonstrated dramatic increases in the population of Mo/Mac in the brain following SCF+G-CSF treatment. SCF+G-CSF treatment robustly increased the transcription of genes implicated in activated immune cells, including gene sets that regulate inflammatory processes and cell migration. SCF+G-CSF treatment also increased a cell population co-expressing microglial and Mo/Mac marker genes. This cell cluster aligned with a disease-associated microglial profile linked with Aß restriction and phagocytosis. S100a8 and S100a9 were the most robustly enhanced genes in both microglial and Mo/Mac clusters following SCF+G-CSF treatment. Furthermore, the topmost genes differentially expressed after SCF+G-CSF treatment were largely upregulated in S100a8/9-positive microglia and Mo/Mac, suggesting a largely well-conserved transcriptional profile related to SCF+G-CSF treatment in cerebral immune cells. This S100a8/9-associated transcriptional profile contained genes related to pro- and anti-inflammatory responses, neuroprotection, and Aß plaque inhibition or clearance. This study sheds new light on the cellular and molecular mechanisms of SCF+G-CSF-mitigated AD neuropathology in the aged brain.

Hippocampus-sensitive and striatum-sensitive learning one month after morphine or cocaine exposure in male rats.

These experiments examined whether morphine and cocaine alter the balance between hippocampal and striatal memory systems measured long after drug exposure. Male rats received injections of morphine (5 mg/kg), cocaine (20 mg/kg), or saline for five consecutive days. One month later, rats were trained to find food on a hippocampus-sensitive place task or a striatum-sensitive response task. Relative to saline controls, morphine-treated rats exhibited impaired place learning but enhanced response learning; prior cocaine exposure did not significantly alter learning on either task. Another set of rats was trained on a dual-solution T-maze that can be solved with either place or response strategies. While a majority (67%) of control rats used place solutions, morphine treatment one month prior resulted in the exclusive use of response solutions (100%). Prior cocaine treatment did not significantly alter strategy selection. Molecular markers related to learning and drug abuse were measured in the hippocampus and striatum one month after drug exposure in behaviorally untested rats. Protein levels of glial-fibrillary acidic protein (GFAP), an intermediate filament specific to astrocytes, increased significantly in the hippocampus after morphine exposure, but not after cocaine exposure. Exposure to morphine or cocaine did not significantly change levels of brain-derived neurotrophic factor (BDNF) or a downstream target of BDNF signaling, glycogen synthase kinase 3ß (GSK3ß), in the hippocampus or striatum. Thus, exposure to morphine resulted in a long-lasting shift from hippocampal toward striatal dominance during learning, an effect that may be associated with lasting alterations in hippocampal astrocytes. Cocaine produced changes in the same direction, suggesting that use of a higher dose or longer duration of exposure might produce effects comparable to those seen with morphine.

Established and new rotavirus vaccines: a comprehensive review for healthcare professionals.

Robust scientific evidence related to two rotavirus (RV) vaccines available worldwide demonstrates their significant impact on RV disease burden. Improving RV vaccination coverage may result in better RV disease control. To make RV vaccination accessible to all eligible children worldwide and improve vaccine effectiveness in high-mortality settings, research into new RV vaccines continues. Although current and in-development RV vaccines differ in vaccine design, their common goal is the reduction of RV disease risk in children <5 years old for whom disease burden is the most significant. Given the range of RV vaccines available, informed decision-making is essential regarding the choice of vaccine for immunization. This review aims to describe the landscape of current and new RV vaccines, providing context for the assessment of their similarities and differences. As data for new vaccines are limited, future investigations will be required to evaluate their performance/added value in a real-world setting.

PLAIN LANGUAGE SUMMARYThe diseaseRotaviruses are a leading cause of acute diarrhea, also called gastroenterities, among young children. They can lead to servere dehydration, hospitilization, and even death.Several vaccines against rotavirus disease have been developed. Their design is based on:weakened human rotavirus that mimic natural infection without causing disease, such as Rotarix, Rotavin-M1, Rotavac and RV3-BB (not yet marketed)non-infective animal viruses such as RotaTeq, Rotasiil or LLR.new concepts, such as inactivated vaccinesWhat is new?We reviewed the current, recently launched and soon-to-be-launched rotavirus vaccines and found that:Rotarix and RotaTeq have been used globally for more than a decade with demonstrated impact and favourable safety profileLimited data on the impact and safety profile are available to date for:Rotavin-M1 and LLR vaccines, locally marketed in Vietnam and China, respectivelyRotavac and Rotasiil, licensed in indiaNew vaccine concepts have been mainly investigated animal models with encouraging resultsWhat is the impact?Despite their different designs, the current rotavirus vaccines demonstrate effectiveness in protecting against rotairus gastroenterits.Data for most recent vacciness are currently limited, for which additional data are needed to demonstrate how they will perform on a larger scale, their added value in a real setting and ther safety profile.

Model Victims of Hate: Victim Blaming in the Context of Islamophobic Hate Crime.

Prior research has explored victim blaming in the context of hate, often depicting hate crime victims as relatively passive recipients of harassment and violence. In reality, victims often do engage with their perpetrators, and the present research explored the effect that victim behavior might have on observer reactions to Islamophobic hate crimes. Participants completed a measure of Islamophobia and read a scenario in which a White man verbally harassed a victim in the park before physically assaulting him. We manipulated both the victim's identity (White or South Asian Muslim) and the victim's response to the perpetrator's verbal harassment (the victim either ignored the offensive comments, verbally reacted to them, or became physically confrontational). When the victim was portrayed as passive and nonresponding, the South Asian Muslim victim attracted lower victim blame, higher perpetrator blame, and increased certainty that the offense was a hate crime. As the victim's behavior became more aggressive, victim blaming increased and perpetrator blaming decreased, but only for the South Asian Muslim victim. It appeared that observers scrutinized the behavior of the South Asian Muslim victim in a way they did not for the White victim, such that sympathy toward the Muslim hate crime victim was tied to his "good behavior." We propose that observers hold expectations of the model hate crime victim, one who is a racialized, religious, or sexual minority who accepts harassment passively and with good behavior; deviation from this script results in a loss of sympathy and an increase in victim blaming. Finally, those higher in Islamophobia displayed reduced perpetrator blame, guilt, and sentences but greater victim blame when the crime targeted a South Asian Muslim as opposed to White victim.

Autobiographical Memory Content and Recollection Frequency: Public Release of Quantitative Datasets and Representative Classification Analysis.

Autobiographical memory (AM), the recollection of personally-experienced events, has several adaptive functions and has been studied across numerous dimensions. We previously introduced two methods to quantify across the life span AM content (the amount and types of retrieved details) and the everyday occurrence of its recollection. The CRAM (cue-recalled autobiographical memory) test used naturalistic word prompts to elicit AMs. Subjects dated the memories to life periods and reported the numbers of details recalled across eight features (e.g., spatial detail, temporal detail, people, and emotions). In separate subjects, an experience sampling method quantified in everyday settings the frequency of AM retrieval and of mental representation of future personal events or actions (termed prospective memory: PM); these data permit evaluation of the temporal orientation of episodic recollection. We describe these datasets now publicly released in open access (CRAM: doi.org/10.6084/m9.figshare.10246958; AM-PM experience-sampling: doi.org/10.6084/m9.figshare.10246940). We also present examples of data mining, using cluster analyses of CRAM (14,242 AMs scored for content from 4,244 subjects). Analysis of raw feature scores yielded three AM clusters separated by total recalled content. Normalizing for total content revealed three classes of AM based on the relative contributions of each feature: AMs containing a relatively large number of details related to people, AMs containing a high degree of spatial information, and AMs with details equally distributed across features. Differences in subject age, memory age, and total content were detected across feature clusters. These findings highlight the value in additional mining of these datasets to further our understanding of autobiographical recollection.

Inactivation of the striatum in aged rats rescues their ability to learn a hippocampus-sensitive spatial navigation task.

Studies of age-related changes in learning and memory often focus on hippocampus-sensitive tasks and reveal age-associated impairments across numerous species and contexts. However, cognitive decline with advanced age is not all-encompassing; for example, forms of striatum-sensitive learning are conserved or enhanced with age. Under certain conditions, hippocampal and striatal memory systems function in opposition. In young adult rodents, disruption of one structure can enhance learning on tasks dependent on the other, suggesting that competitive interactions across memory systems contribute to learning and memory abilities. This report examines whether imbalances across memory systems might contribute to cognitive aging. We inactivated the striatum using central infusions of lidocaine (sodium channel blocker) prior to hippocampus-sensitive spatial (place) training in young (3-4-month-old) and old (24-25-month-old) F344 male rats. Consistent with prior work, vehicle-infused old rats exhibited place learning impairments relative to young rats. Additionally, striatal inactivation enhanced learning in old rats, but not young rats, abolishing the age-related impairment. These findings suggest that age-related declines in learning tasks thought to engage the hippocampus may stem from exaggerated interference from other memory systems and that interventions to target the striatum may reverse some age-related learning decrements.

Defining and Predicting Opioid and Cocaine Treatment Response.

Background: Treatment with methadone is effective in reducing heroin use, HIV risk, and death; however, not all patients respond to treatment. Better outcomes may emerge with personalized treatment based on factors that influence treatment courses. Objectives: To investigate psychosocial variables contributing to treatment response, using a comprehensive definition of treatment response. Methods: Seventy participants seeking treatment for heroin and cocaine addiction completed up to 40 weeks of daily methadone. At week 22, we administered a semi-structured interview for DSM-IV symptoms. We defined opioid treatment responders as people still enrolled at 22 weeks, not meeting past 30-day criteria for DSM-IV opioid abuse or dependence or DSM-5 opioid use disorder, and providing ≥75% opioid-negative urine samples in the 30 days prior to week 22. The same criteria were applied to assess cocaine treatment response. Results: Sample was 71% male, 41% White, and averaged 39.4 ± 7.9 years old. Opioid treatment response was more likely in participants who had been employed over the past 3 years (OR: 8.1, 95% CI: 1.2-55) and less likely in those who spent more time on hobbies (OR: 0.45, 95% CI: 0.23-0.88). Cocaine treatment response was more likely in participants who had a good relationship with their father (OR: 5.3, 95% CI: 1.2-24) and less likely if positive for hepatitis C (OR: 0.15, 95% CI: 0.03-0.75). Conclusions: Pretreatment characteristics differentially predict treatment response for heroin and cocaine use. Similar research in diverse patient groups may aid in the development of personalized treatment combining biologic treatment with targeted psychosocial interventions.

Boosting Abscopal Response to Radiotherapy with Sargramostim: A Review of Data and Ongoing Studies.

Drug development in oncology today routinely focuses on approaches that utilize the patients' immune system to destroy the malignancy. Combinatorial approaches of antineoplastic agents, both new and old, are being incorporated in the armamentarium of cancer treatments. The overarching goal of therapy remains the achievement of a complete and durable response with long term remission or cure. One approach in advancing treatment is aimed at strategies that improve immunological memory to induce long lasting immunity against the tumor. Although radiation therapy has not traditionally been thought to elicit an immunological effect, an increasing number of reports document the induction of an immune response against a tumor that kills cancer cells distant to the original site of treatment after local irradiation to a tumor. This phenomenon is called an abscopal effect. Since radiation alone is rarely associated with such a response, it is being combined with immuno-oncology drugs in an attempt to enhance response. One such strategy combines sargramostim, a recombinant human granulocyte macrophage colony stimulating factor (rhu GM-CSF), with radiotherapy. GM-CSF is a cytokine secreted by multiple cells types that promotes maturation of dendritic cells and enables the presentation of tumor-associated antigens to generate a T-cell response. This review article discusses the outcomes of clinical trials and case reports examining the efficacy and safety of combining radiation therapy with this immunomodulatory agent. We will also examine future studies and challenges facing the translation of this therapeutic approach.

Involvement of lactate transport in two object recognition tasks that require either the hippocampus or striatum.

Growing evidence indicates that hippocampal lactate, released from astrocytes, is an important regulator of learning and memory processing. This study evaluated the selective involvement of hippocampal and striatal lactate in two object recognition tasks. The tasks tested recognition memory after a change in location of two target objects (double object location; dOL) or after replacement of familiar targets with two new objects set in the original locations (double object replacement; dOR). Rats received three study sessions across which exploration times decreased. The recognition index was the change in exploration time of both objects on a test trial from the exploration times on the final study trial. We first verified a double dissociation between hippocampus and striatum across these tasks. The sodium channel blocker, lidocaine, was infused into one of the two brain regions after the study sessions and before the test trial. To test the role of neuronal lactate in recognition memory, an inhibitor of the neuronal lactate transporter, α-cyano-4-hydroxycinnamate (4-CIN), was similarly infused. For both drugs, infusions into the hippocampus but not the striatum impaired recognition in the dOL, whereas infusions into the striatum but not hippocampus impaired recognition in the dOR. The findings obtained with 4-CIN demonstrate for the first time the importance of neuronal lactate uptake in the hippocampus and the striatum for object recognition memory processing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Predicting opioid use disorder in patients with chronic pain who present to the emergency department.

BACKGROUND: Emergency department (ED) patients with chronic pain challenge providers to make quick and accurate assessments without an in-depth pain management consultation. Emergency physicians need reliable means to determine which patients may receive opioid therapy without exacerbating opioid use disorder (OUD). METHODS: Eighty-nine ED patients with a chief complaint of chronic pain were enrolled. Researchers administered questionnaires and reviewed medical and state prescription monitoring database information. Participants were classified as either OUD or non-OUD. Statistical analysis included a bivariate analysis comparing differences between groups and multivariate logistic regression evaluating ORs. RESULTS: The 45 participants categorised as OUD had a higher proportion of documented or reported psychiatric diagnoses (p=0.049), preference of opioid treatment (p=0.005), current oxycodone prescription (p=0.043), borrowed pain medicine (p=0.004) and non-authorised dose increase (p<0.001). The state prescription monitoring database revealed the OUD group to have an increased number of opioid prescriptions (p=0.005) and pills (p=0.010). Participants who borrowed pain medicine and engaged in non-authorised dose increase were 5.2 (p=0.025, 95% CI 1.24 to 21.9) and 6.1 times (p=0.001, 95% CI 1.55 to 24.1) more likely to have OUD, respectively. LIMITATIONS: Major limitations of our study include a small sample size, self-reported measures and convenience sample which may introduce selection bias. CONCLUSION: Patients with chronic pain with OUD have distinguishable characteristics. Emergency physicians should consider such evidence-based variables prior to opioid therapy to ameliorate the opioid crisis and limit implicit bias.

Evaluating the effectiveness and reliability of the Vibrant Soundbridge and Bonebridge auditory implants in clinical practice: Study design and methods for a multi-centre longitudinal observational study.

BACKGROUND: The Vibrant Soundbridge middle ear implant and the Bonebridge bone conducting hearing device are hearing implants that use radio frequency transmission to send information from the sound processor to the internal transducer. This reduces the risk of skin problems and infection but requires a more involved surgical procedure than competitor skin penetrating devices. It is not known whether more complex surgery will lead to additional complications. There is little information available on the reliability of these systems and adverse medical or surgical events. The primary research question is to determine the reliability and complication rate for the Vibrant Soundbridge and Bonebridge. The secondary research question explores changes in quality of life following implantation of the devices. The tertiary research question looks at effectiveness via changes in auditory performance. METHOD: The study was designed based on a combination of a literature search, two clinician focus groups and expert review.A multi-centre longitudinal observational study was designed. There are three study groups, two will have been implanted prior to the start of the study and one group, the prospective group, will be implanted after initiation of the study. Outcomes are surgical questionnaires, measures of quality of life, user satisfaction and speech perception tests in quiet and in noise. CONCLUSION: This is the first multi-centre study to look at these interventions and includes follow up over time to understand effectiveness, reliability, quality of life and complications.

A review of recommendations for rotavirus vaccination in Europe: Arguments for change.

BACKGROUND: More than 10 years after the authorisation of two rotavirus vaccines of demonstrated efficacy and with a strongly positive benefit-risk profile, uptake in Europe remains low. Only 13 countries in Europe provide a fully-funded rotavirus universal mass vaccination (UMV) programme, three provide a partially-funded programme, and one provides full funding for a reduced programme targeting at-risk infants. Around 40% of countries in Europe currently have no existing recommendations for rotavirus vaccine use in children from the national government. METHODS: We provide an overview of the status of rotavirus vaccine recommendations across Europe and the factors impeding uptake. We consider the evidence for the benefits and risks of vaccination, and argue that cost-effectiveness and cost-saving benefits justify greater access to rotavirus vaccines for infants living in Europe. RESULTS: Lack of awareness of the direct and indirect burden caused by rotavirus disease, potential cost-saving from rotavirus vaccination including considerable benefits to children, families and society, and government/insurer cost constraints all contribute to complacency at different levels of health policy in individual countries. CONCLUSIONS: More than 10 years after their introduction, available data confirm the benefits and acceptable safety profile of infant rotavirus UMV programmes. Europe serves to gain considerably from rotavirus UMV in terms of reductions in healthcare resource utilization and related costs in both vaccinated subjects and their unvaccinated siblings through herd protection.

Comparison of warm season and cool season forages for dairy grazing systems in continuous culture.

The objective of this study was to compare warm-season annual grasses to cool-season perennial (CSP) grasses for ruminal nutrient digestibility and N metabolism in a dual-flow continuous culture fermentation system. Dietary treatments were 1) fresh alfalfa, 2) CSP grasses and legumes, 3) brown-midrib sorghum-sudangrass (BMRSS), and 4) teff grass from an organic dairy production system. Eight dual-flow continuous culture fermenters were used during two consecutive 10-d periods consisting of 7 d for stabilization followed by 3 d of sampling. Fermenter samples were collected on days 8, 9, and 10 for analysis of pH, NH3-N, and VFA. Apparent DM, OM, NDF, and ADF digestibility were on average lesser (P < 0.05) in CSP grasses and legumes and warm-season annual grasses compared with alfalfa. True DM and OM digestibility were lesser (P < 0.05) for CSP grasses and legumes and warm-season annual grasses compared with fresh alfalfa. Total VFA were not affected (P > 0.05) by forage. The NH3-N concentrations were highest (P < 0.05) with alfalfa compared with the other CSP grasses and legumes and warm-season annual grasses. CP digestibility was not affected (P > 0.05) by forage treatment. Flow of NH3-N was greatest (P < 0.05) for alfalfa, reflecting the greatest NH3-N concentration. Flow of total N was greatest (P < 0.05) for alfalfa, intermediate for teff, and lowest for CSP grasses and legumes and BMRSS. Flows of bacterial N, efficiency of bacterial N, non-NH3-N, and dietary N were not affected (P > 0.05) by forage source. Overall, fermentation of warm-season grasses was similar to the cool-season grasses and legumes which indicate dairy producers may use warm-season grasses without concerns about negative impact on rumen health.

Using life cycle assessment and techno-economic analysis in a real options framework to inform the design of algal biofuel production facilities.

This study investigates the use of "real options analysis" (ROA) to quantify the value of greater product flexibility at algal biofuel production facilities. A deterministic optimization framework is integrated with a combined life cycle assessment/techno-economic analysis model and subjected to an ensemble of 30-year commodity price trajectories. Profits are maximized for two competing plant configurations: 1) one that sells lipid-extracted algae as animal feed only; and 2) one that can sell lipid-extracted algae as feed or use it to recover nutrients and energy, due to an up-front investment in anaerobic digestion/combined heat and power. Results show that added investment in plant flexibility does not result in an improvement in net present value, because current feed meal prices discourage use of lipid-extracted algae for nutrient and energy recovery. However, this study demonstrates that ROA provides many useful insights regarding plant design that cannot be captured via traditional techno-economic modeling.

Evaluating the relative impacts of operational and financial factors on the competitiveness of an algal biofuel production facility.

Algal biofuels are becoming more economically competitive due to technological advances and government subsidies offering tax benefits and lower cost financing. These factors are linked, however, as the value of technical advances is affected by modeling assumptions regarding the growth conditions, process design, and financing of the production facility into which novel techniques are incorporated. Two such techniques, related to algal growth and dewatering, are evaluated in representative operating and financing scenarios using an integrated techno-economic model. Results suggest that these techniques can be valuable under specified conditions, but also that investment subsidies influence cost competitive facility design by incentivizing development of more capital intensive facilities (e.g., favoring hydrothermal liquefaction over transesterification-based facilities). Evaluating novel techniques under a variety of operational and financial scenarios highlights the set of site-specific conditions in which technical advances are most valuable, while also demonstrating the influence of subsidies linked to capital intensity.

Chromosomes and clinical anatomy.

Chromosome abnormalities may cast light on the nature of mechanisms whereby normal anatomy evolves, and abnormal anatomy arises. Correlating genotype to phenotype is an exercise in which the geneticist and the anatomist can collaborate. The increasing power of the new genetic methodologies is enabling an increasing precision in the delineation of chromosome imbalances, even to the nucleotide level; but the classical skills of careful observation and recording remain as crucial as they always have been. Clin. Anat. 29:540-546, 2016. © 2016 Wiley Periodicals, Inc.