Acute and circadian feedforward regulation of agouti-related peptide hunger neurons.

When food is freely available, eating occurs without energy deficit. While agouti-related peptide (AgRP) neurons are likely involved, their activation is thought to require negative energy balance. To investigate this, we implemented long-term, continuous in vivo fiber-photometry recordings in mice.

Multiple Goals Theory and Communication Quality Analysis for Fellows Communication Training.

Background: End-of-life communication skills are vital to high-quality critical care. Patients and families often report deficiencies in end-of-life communication by providers. However, formalized training is difficult to implement and study on a large scale.

Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding.

Brief stimuli can trigger longer-lasting brain states. G-protein-coupled receptors (GPCRs) could help sustain such states by coupling slow-timescale molecular signals to neuronal excitability. Brainstem parabrachial nucleus glutamatergic (PBN) neurons regulate sustained brain states such as pain and express G-coupled GPCRs that increase cAMP signaling.

Competition between stochastic neuropeptide signals calibrates the rate of satiation.

We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and αMSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP. How cAMP integrates opposing peptide signals to regulate energy balance, and the spatiotemporal dynamics of endogenous peptidergic signaling, remain largely unknown.

A synaptic amplifier of hunger for regaining body weight in the hypothalamus.

Restricting caloric intake effectively reduces body weight, but most dieters fail long-term adherence to caloric deficit and eventually regain lost weight. Hypothalamic circuits that control hunger drive critically determine body weight; yet, how weight loss sculpts these circuits to motivate food consumption until lost weight is regained remains unclear. Here, we probe the contribution of synaptic plasticity in discrete excitatory afferents on hunger-promoting AgRP neurons.

Transient cAMP production drives rapid and sustained spiking in brainstem parabrachial neurons to suppress feeding.

Brief stimuli can trigger longer lasting brain states. G protein-coupled receptors (GPCRs) could help sustain such states by coupling slow-timescale molecular signals to neuronal excitability. Brainstem parabrachial nucleus glutamatergic neurons (PBN ) regulate sustained brain states such as pain, and express G -coupled GPCRs that increase cAMP signaling.

Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes.

Insulin-induced hypoglycemia is a major treatment barrier in type-1 diabetes (T1D). Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon. Varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (8 to 4 mM) has no significant effect on glucagon secretion in the perfused mouse pancreas or in isolated mouse islets (in vitro), and yet associates with dramatic increases in plasma glucagon.

Neural basis for regulation of vasopressin secretion by anticipated disturbances in osmolality.

Water balance, tracked by extracellular osmolality, is regulated by feedback and feedforward mechanisms. Feedback regulation is reactive, occurring as deviations in osmolality are . Feedforward or presystemic regulation is proactive, occurring when disturbances in osmolality are .

Food cue regulation of AGRP hunger neurons guides learning.

Agouti-related peptide (AGRP)-expressing neurons are activated by fasting-this causes hunger, an aversive state that motivates the seeking and consumption of food. Eating returns AGRP neuron activity towards baseline on three distinct timescales: rapidly and transiently following sensory detection of food cues, slowly and longer-lasting in response to nutrients in the gut, and even more slowly and permanently with restoration of energy balance. The rapid regulation by food cues is of particular interest as its neurobiological basis and purpose are unknown.

Impact of Body Mass Index on COVID-19-Related In-Hospital Outcomes and Mortality.

Background: Given the high prevalence of obesity around the globe, patients with coronavirus disease 2019 (COVID-19) are at an increased risk of devastating complications.

Methods: A retrospective cohort study was performed to determine the association of basal metabolic index (body mass index (BMI)) with the need for invasive mechanical ventilation (IMV), dialysis, upgrade to an intensive care unit (ICU) and mortality. Independent -test and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aORs) with its 95% confidence interval (CI), respectively.

Anticoagulation in COVID-19: a single-center retrospective study.

COVID-19 induces a pro-thrombotic state as evidenced by microvascular thrombi in the renal and pulmonary vasculature. Therapeutic anticoagulation in COVID-19 has been debated and data remain anecdotal. We hypothesize that therapeutic anticoagulation is associated with a reduction in in-hospital mortality, upgrade to intensive care unit, invasive mechanical ventilation, and acute renal failure necessitating dialysis by decreasing the over-all clot burden.

Predictability of CRP and D-Dimer levels for in-hospital outcomes and mortality of COVID-19.

Background: Systemic inflammation elicited by a cytokine storm is considered a hallmark of coronavirus disease 2019 (COVID-19). This study aims to assess the clinical utility of the C-reactive protein (CRP) and D-Dimer levels for predicting in-hospital outcomes in COVID-19.

Methods: A retrospective cohort study was performed to determine the association of CRP and D-Dimer with the need for invasive mechanical ventilation (IMV), dialysis, upgrade to an intensive care unit (ICU) and mortality.

Hamman-Rich Syndrome: A Diagnosis of Exclusion in the COVID-19 Pandemic.

Hamman-Rich syndrome is a rapidly progressive interstitial lung disease with acute respiratory distress syndrome physiology. It carries a grave prognosis and a high early mortality rate. It is often distinguished from other similar pulmonary pathologies based on the clinical course, laboratory findings, bronchoalveolar lavage testing, and pathology report.

Incidence of Multidrug Resistant Infections in Emergency Department Patients with Suspected Sepsis.

Background: Inappropriate antibiotic therapy in sepsis is associated with poor outcomes, clinicians often provide routine coverage for multidrug resistant (MDR) bacteria. However, these regimens may contribute to problems related to antibiotic overuse. To understand the incidence and related factors of multidrug resistant bacterial infections in ED patients with sepsis, we examined how often patients with sepsis in our emergency department had MDR infections.

Lymphocyte-to-C-Reactive Protein Ratio: A Novel Predictor of Adverse Outcomes in COVID-19.

Background: Systemic inflammation elicited by a cytokine storm is considered a hallmark of coronavirus disease 2019 (COVID-19). This study aims to assess the validity and clinical utility of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR), typically used for gastric carcinoma prognostication, versus the neutrophil-to-lymphocyte ratio (NLR) for predicting in-hospital outcomes in COVID-19.

Methods: A retrospective cohort study was performed to determine the association of LCR and NLR with the need for invasive mechanical ventilation (IMV), dialysis, upgrade to an intensive care unit (ICU) and mortality.

Leptin's hunger-suppressing effects are mediated by the hypothalamic-pituitary-adrenocortical axis in rodents.

Leptin informs the brain about sufficiency of fuel stores. When insufficient, leptin levels fall, triggering compensatory increases in appetite. Falling leptin is first sensed by hypothalamic neurons, which then initiate adaptive responses.

Lateral hypothalamic neurotensin neurons promote arousal and hyperthermia.

Sleep and wakefulness are greatly influenced by various physiological and psychological factors, but the neuronal elements responsible for organizing sleep-wake behavior in response to these factors are largely unknown. In this study, we report that a subset of neurons in the lateral hypothalamic area (LH) expressing the neuropeptide neurotensin (Nts) is critical for orchestrating sleep-wake responses to acute psychological and physiological challenges or stressors. We show that selective activation of NtsLH neurons with chemogenetic or optogenetic methods elicits rapid transitions from non-rapid eye movement (NREM) sleep to wakefulness and produces sustained arousal, higher locomotor activity (LMA), and hyperthermia, which are commonly observed after acute stress exposure.

Ventrolateral periaqueductal gray mediates rapid eye movement sleep regulation by melanin-concentrating hormone neurons.

Neurons containing melanin-concentrating hormone (MCH) in the lateral hypothalamic area (LH) have been shown to promote rapid eye movement sleep (REMs) in mice. However, the downstream neural pathways through which MCH neurons influence REMs remained unclear. Because MCH neurons are considered to be primarily inhibitory, we hypothesized that these neurons inhibit the midbrain 'REMs-suppressing' region consisting of the ventrolateral periaqueductal gray and the lateral pontine tegmentum (vlPAG/LPT) to promote REMs.

The Paraventricular Hypothalamus Regulates Satiety and Prevents Obesity via Two Genetically Distinct Circuits.

SIM1-expressing paraventricular hypothalamus (PVH) neurons are key regulators of energy balance. Within the PVH population, melanocortin-4 receptor-expressing (PVH) neurons are known to regulate satiety and bodyweight, yet they account for only half of PVH neuron-mediated regulation. Here we report that PVH prodynorphin-expressing (PVH) neurons, which notably lack MC4Rs, function independently and additively with PVH neurons to account for the totality of PVH neuron-mediated satiety.

Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity.

Synaptotagmin-11 (Syt11) is a Synaptotagmin isoform that lacks an apparent ability to bind calcium, phospholipids, or SNARE proteins. While human genetic studies have linked mutations in the gene to schizophrenia and Parkinson's disease, the localization or physiological role of Syt11 remain unclear. We found that in neurons, Syt11 resides on abundant vesicles that differ from synaptic vesicles and resemble trafficking endosomes.