Development of a Deep Learning Network to Classify Inferior Vena Cava Collapse to Predict Fluid Responsiveness.

Objectives: To create a deep learning algorithm capable of video classification, using a long short-term memory (LSTM) network, to analyze collapsibility of the inferior vena cava (IVC) to predict fluid responsiveness in critically ill patients.

Methods: We used a data set of IVC ultrasound (US) videos to train the LSTM network. The data set was created from IVC US videos of spontaneously breathing critically ill patients undergoing intravenous fluid resuscitation as part of 2 prior prospective studies.

Predictive Models for Very Preterm Birth: Developing a Point-of-Care Tool.

Objective: The objective of this study was to create three point-of-care predictive models for very preterm birth using variables available at three different time points: prior to pregnancy, at the end of the first trimester, and mid-pregnancy.

Study Design: This is a retrospective cohort study of 359,396 Ohio Medicaid mothers from 2008 to 2015. The last baby for each mother was included in the final dataset.

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

Introduction: Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited.

Objectives: The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis.

Unusual behaviour induced by phase separation in hydrogel microspheres.

Unlabelled: Hydrogel microspheres with the capability to interact with charged species such as various drugs by ion-exchange processes are useful in a variety of biomedical applications. Such systems have been developed to allow active loading of the microsphere with chemotherapeutic agents in the hospital pharmacy for subsequent locoregional therapy of tumours in the liver by drug-eluting bead chemoembolization (DEB-TACE). A variety of microspherical embolisation systems have been described, all based upon hydrogels bearing anionic functionalities to allow interaction with cationically charged drugs.

Transforming growth factor β recruits persistent MAPK signaling to regulate long-term memory consolidation in Aplysia californica.

In this study, we explore the mechanistic relationship between growth factor signaling and kinase activity that supports the protein synthesis-dependent phase of long-term memory (LTM) consolidation for sensitization ofAplysia Specifically, we examine LTM for tail shock-induced sensitization of the tail-elicited siphon withdrawal (T-SW) reflex, a form of memory that requires both (i) extracellular signal-regulated kinase (ERK1/2; MAPK) activity within identified sensory neurons (SNs) that mediate the T-SW and (ii) the activation of transforming growth factor β (TGFβ) signaling. We now report that repeated tail shocks that induce intermediate-term (ITM) and LTM for sensitization, also induce a sustained post-training phase of MAPK activity in SNs (lasting at least 1 h). We identified two mechanistically distinct phases of post-training MAPK: (i) an immediate phase that does not require ongoing protein synthesis or TGFβ signaling, and (ii) a sustained phase that requires both protein synthesis and extracellular TGFβ signaling.

Reelin protects against amyloid β toxicity in vivo.

Alzheimer's disease (AD) is a currently incurable neurodegenerative disorder and is the most common form of dementia in people over the age of 65 years. The predominant genetic risk factor for AD is the ε4 allele encoding apolipoprotein E (ApoE4). The secreted glycoprotein Reelin enhances synaptic plasticity by binding to the multifunctional ApoE receptors apolipoprotein E receptor 2 (Apoer2) and very low density lipoprotein receptor (Vldlr).

Distinct Growth Factor Families Are Recruited in Unique Spatiotemporal Domains during Long-Term Memory Formation in Aplysia californica.

Several growth factors (GFs) have been implicated in long-term memory (LTM), but no single GF can support all of the plastic changes that occur during memory formation. Because GFs engage highly convergent signaling cascades that often mediate similar functional outcomes, the relative contribution of any particular GF to LTM is difficult to ascertain. To explore this question, we determined the unique contribution of distinct GF families (signaling via TrkB and TGF-βr-II) to LTM formation in Aplysia.

Latent memory facilitates relearning through molecular signaling mechanisms that are distinct from original learning.

A highly conserved feature of memory is that it can exist in a latent, non-expressed state which is revealed during subsequent learning by its ability to significantly facilitate (savings) or inhibit (latent inhibition) subsequent memory formation. Despite the ubiquitous nature of latent memory, the mechanistic nature of the latent memory trace and its ability to influence subsequent learning remains unclear. The model organism Aplysia californica provides the unique opportunity to make strong links between behavior and underlying cellular and molecular mechanisms.

More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration.

Members of the low-density lipoprotein (LDL) receptor gene family have a diverse set of biological functions that transcend lipid metabolism. Lipoprotein receptors have broad effects in both the developing and adult brain and participate in synapse development, cargo trafficking, and signal transduction. In addition, several family members play key roles in Alzheimer's disease (AD) pathogenesis and neurodegeneration.

Overcoming dose limitations using the orbital(®) multi-breath dry powder inhaler.

Purpose: A new approach to delivering high doses of dry powder medicaments to the lung is presented. The Orbital(®) dry powder device is designed to deliver high doses of drugs to the respiratory tract in a single dosing unit, via multiple inhalation maneuvers, overcoming the need to prime or insert multiple capsules.

Methods: The Orbital was tested in its prototype configuration and compared with a conventional RS01 capsule device.

Pattern and predictability in memory formation: from molecular mechanisms to clinical relevance.

Most long-term memories are formed as a consequence of multiple experiences. The temporal spacing of these experiences is of considerable importance: experiences distributed over time (spaced training) are more easily encoded and remembered than either closely spaced experiences, or a single prolonged experience (massed training). In this article, we first review findings from studies in animal model systems that examine the cellular and molecular properties of the neurons and circuits in the brain that underlie training pattern sensitivity during long-term memory (LTM) formation.

MAPK establishes a molecular context that defines effective training patterns for long-term memory formation.

Although the importance of spaced training trials in the formation of long-term memory (LTM) is widely appreciated, surprisingly little is known about the molecular mechanisms that support interactions between individual trials. The intertrial dynamics of ERK/MAPK activation have recently been correlated with effective training patterns for LTM. However, whether and how MAPK is required to mediate intertrial interactions remains unknown.

Bleeding risk factors associated with argatroban therapy in the critically ill.

Argatroban is a parenteral direct thrombin inhibitor labeled for anticoagulation in patients with confirmed or suspected heparin-induced thrombocytopenia in the United States. Currently there are no studies evaluating bleeding risk factors in Intensive Care Unit patients.To determine bleeding risk factors associated with argatroban therapy in the critically ill.

The association between body mass index, processes of care, and outcomes from mechanical ventilation: a prospective cohort study.

Objective: To determine the association between excess weight and processes of care and outcomes for critically ill adults.

Design: Prospective cohort study.

Setting: Three medical intensive care units at two hospitals.

The tail-elicited tail withdrawal reflex of Aplysia is mediated centrally at tail sensory-motor synapses and exhibits sensitization across multiple temporal domains.

The defensive withdrawal reflexes of Aplysia californica have provided powerful behavioral systems for studying the cellular and molecular basis of memory formation. Among these reflexes the tail-elicited tail withdrawal reflex (T-TWR) has been especially useful. In vitro studies examining the monosynaptic circuit for the T-TWR, the tail sensory-motor (SN-MN) synapses, have identified the induction requirements and molecular basis of different temporal phases of synaptic facilitation that underlie sensitization in this system.

Vocal cord dysfunction: beyond severe asthma.

Background: Vocal cord dysfunction (VCD) is the abnormal adduction of the vocal cords during inspiration causing extrathoracic airway obstruction. VCD has been described as a confounder of severe asthma. The influence of VCD among less severe asthmatics has not been previously defined.

It's all about timing.

In the formation of long-term memories, a "spaced" distribution of study sessions is more beneficial than closely spaced "massed" study sessions. Pagani et al. (2009) examine the molecular basis of this spacing effect in Drosophila and find a role for the SHP2 homolog, corkscrew, an activator of Ras/MAPK signaling, in establishing optimal spacing intervals.

The clinical utility of eucapnic voluntary hyperventilation testing for the diagnosis of exercise-induced bronchospasm.

Background: Exercise-induced bronchospasm (EIB) is the acute, transient airway narrowing associated with exercise. Eucapnic voluntary hyperventilation (EVH) has been used to diagnose EIB in elite athletes and in research settings. The clinical utility of EVH in a general pulmonary practice has not previously been reported.

Transient mitogen-activated protein kinase activation is confined to a narrow temporal window required for the induction of two-trial long-term memory in Aplysia.

Although it is commonly appreciated that spaced training is superior to massed training in memory formation, the molecular mechanisms underlying this feature of memory are largely unknown. We previously described the selective benefit of multiple spaced (vs massed) training trials in the induction of long-term memory (LTM) for sensitization in Aplysia californica. We now report that LTM can be induced with only two spaced training trials [tail shocks (TSs)] when the second TS is administered 45 min after the first.

Quantification of fat mobilization in patients undergoing coronary artery revascularization using off-pump and on-pump techniques.

Fat mobilization during cardiopulmonary bypass (CPB) is a recognized risk of the procedure. Intravascular mobilization of fat emboli subsequent to CPB has been implicated in some of its recognized pathophysiologies, particularly with regard to cerebral embolic injury. The aim of this study was to investigate whether fat mobilization is still a real issue in modern perfusion practice and to determine whether off pump coronary artery bypass techniques minimize this risk.

Immune competence of cancer-reactive T cells generated de novo in adult tumor-bearing mice.

The impact of timing of antigen introduction into fetus and neonates leads to the suggestion that pre-existing antigens are tolerogenic to immunocompetent cells generated thereafter. This hypothesis predicts that in patients with cancer who are undergoing bone marrow transplantation, newly produced T cells with specificity for pre-existing tumor cells will be inactivated by the tumor antigens in the host. Because the effect of tumor cells on developing cancer-reactive T cells has not been investigated, we set out to systematically analyze the impact of tumor cells in the periphery on the development of tumor-reactive T cells in the thymus and their immunocompetence in the periphery.

Latent memory for sensitization in Aplysia.

In the analysis of memory it is commonly observed that, even after a memory is apparently forgotten, its latent presence can still be revealed in a subsequent learning task. Although well established on a behavioral level, the mechanisms underlying latent memory are not well understood. To begin to explore these mechanisms, we have used Aplysia, a model system that permits the simultaneous study of memory at the behavioral, cellular, and molecular levels.

Multiple requirements for Hes 1 during early eye formation.

During embryogenesis, multiple developmental processes are integrated through their precise temporal regulation. Hes1 is a transcriptional repressor that regulates the timing of mammalian retinal neurogenesis. However, roles for Hes1 in early eye development have not been well defined.

Precocious retinal neurons: Pax6 controls timing of differentiation and determination of cell type.

The transcription factor Pax6 plays a pivotal role in eye development, as eye morphogenesis is arrested at a primitive optic vesicle stage in homozygous Pax6 mutant mouse embryos. The arrested optic vesicle development has led to the assumption that cellular differentiation programs are unable to initiate. Contrary to this, we found that neurogenesis in Pax6 mutant optic vesicles was not arrested, but instead accelerated as numerous neurons differentiated precociously, more than a day earlier than normal.

Effects of selective inhibitors of nitric oxide synthase-2 dimerization on acute cardiac allograft rejection.

Background: Nitric oxide synthase-2 (NOS2) is expressed during acute cardiac allograft rejection in association with myocardial inflammation, contractile dysfunction, and death of cardiomyocytes by necrosis and apoptosis. Recently, allosteric inhibitors of NOS2 monomer dimerization that block NOS2 activity have been developed.

Methods And Results: To investigate effects of selective NOS2 blockade, 15 mg/kg of BBS-1 or BBS-2 was administered twice daily subcutaneously to rats starting the day of heterotopic heart transplantation.