Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use.

Objectives: To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis.

Design: Prospective cohort study.

Setting: Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington.

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

Background: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy.

Research Question: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19?

Study Design And Methods: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473).

Damage to the dorsolateral prefrontal cortex is associated with repetitive compulsive behaviors in patients with penetrating brain injury.

Background: Damage to cortico-striato-thalamo-cortical (CSTC) circuits is associated with the development of repetitive behaviours in animals and humans. However, the types of repetitive behaviours that are developed after injury to these structures are poorly defined. This study examines the effect of damage to separate elements of CSTC circuits sustained by veterans of the Vietnam War on obsessions, compulsions, and tics.

Towards Defining the Neuroanatomical Basis of Late-Onset Psychiatric Symptoms.

Psychiatric symptoms, including changes in emotional processing, are a common feature of many neurodegenerative disorders, such as Alzheimer's disease, dementia with Lewy Bodies, frontotemporal dementia, and Huntington's disease. However, the neuroanatomical basis of emotional symptoms is not well defined; this stands in contrast to the relatively well-understood neuroanatomical correlates of cognitive and motor symptoms in neurodegenerative disorders. Furthermore, psychiatric diagnostic categories, as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Statistical Classification of Diseases and Related Health Problems (ICD), may have limited applicability in patients with late-onset psychiatric symptoms in the context of neurodegenerative disorders.

Establishing a Cohort and a Biorepository to Identify Biomarkers for Early Detection of Lung Cancer: The Nashville Lung Cancer Screening Trial Cohort.

A prospective longitudinal cohort of individuals at high risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer. The goal of this study is to characterize individuals with high risk for lung cancer, accumulating valuable biospecimens and LDCT chest scans longitudinally over 5 years. Participants 55-80 years of age with a 5-year estimated risk of developing lung cancer >1.

Tolcapone Treatment for Cognitive and Behavioral Symptoms in Behavioral Variant Frontotemporal Dementia: A Placebo-Controlled Crossover Study.

Background: There are currently no disease-targeted treatments for cognitive or behavioral symptoms in patients with behavioral variant frontotemporal dementia (bvFTD).

Objective: To determine the effect of tolcapone, a specific inhibitor of Catechol-O-Methyltransferase (COMT), in patients with bvFTD.

Methods: In this randomized, double-blind, placebo-controlled, cross-over study at two study sites, we examined the effect of tolcapone on 28 adult outpatients with bvFTD.

Effect of Functional BDNF and COMT Polymorphisms on Symptoms and Regional Brain Volume in Frontotemporal Dementia and Corticobasal Syndrome.

Objective: The authors examined the effects of two common functional polymorphisms-brain-derived neurotrophic factor (BDNF) Val66Met and catechol--methyltransferase (COMT) Val158Met-on cognitive, neuropsychiatric, and motor symptoms and MRI findings in persons with frontotemporal lobar degeneration (FTLD) syndromes.

Methods: The BDNF Val66Met and COMT Val158Met polymorphisms were genotyped in 174 participants with FTLD syndromes, including behavioral variant frontotemporal dementia, primary progressive aphasia, and corticobasal syndrome. Gray matter volumes and scores on the Delis-Kaplan Executive Function System, Mattis Dementia Rating Scale, Wechsler Memory Scale, and Neuropsychiatric Inventory were compared between allele groups.

Six-minute walk distance in healthy young adults.

Background: The 6-min walk test (6MWT) is a commonly used clinical assessment of exercise capacity in patients with cardiopulmonary or neuromuscular disease, but normal values are lacking for young adults, who are frequent subjects of testing.

Methods: In a two-center study, 272 young adults, ages 18-50, underwent American Thoracic Society protocolized 6-min walk testing, and 56 underwent repeat testing. A linear regression model was developed based on anthropomorphic data.

Acute cerebellar knockdown of reproduces salient features of myoclonus-dystonia (DYT11) in mice.

Myoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations in and characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-specific developmental compensation mechanisms, which have limited the study of neural mechanisms underlying DYT11. To circumvent potential compensation, we used short hairpin RNA (shRNA) to acutely knock down S in the adult mouse and found that this approach produced dystonia and repetitive, myoclonic-like, jerking movements in mice that improved after administration of ethanol.

Derivation and validation of a two-biomarker panel for diagnosis of ARDS in patients with severe traumatic injuries.

Background: Acute respiratory distress syndrome (ARDS) is common after severe traumatic injuries but is underdiagnosed and undertreated. We hypothesized that a panel of plasma biomarkers could be used to diagnose ARDS in severe trauma. To test this hypothesis, we derived and validated a biomarker panel in three independent cohorts and compared the diagnostic performance to clinician recognition of ARDS.

It's not just the basal ganglia: Cerebellum as a target for dystonia therapeutics.

Dystonia is a common movement disorder that devastates the lives of many patients, but the etiology of this disorder remains poorly understood. Dystonia has traditionally been considered a disorder of the basal ganglia. However, growing evidence suggests that the cerebellum may be involved in certain types of dystonia, raising several questions.

A role for cerebellum in the hereditary dystonia DYT1.

DYT1 is a debilitating movement disorder caused by loss-of-function mutations in torsinA. How these mutations cause dystonia remains unknown. Mouse models which have embryonically targeted torsinA have failed to recapitulate the dystonia seen in patients, possibly due to differential developmental compensation between rodents and humans.

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia.

A role for the cerebellum in causing ataxia, a disorder characterized by uncoordinated movement, is widely accepted. Recent work has suggested that alterations in activity, connectivity, and structure of the cerebellum are also associated with dystonia, a neurological disorder characterized by abnormal and sustained muscle contractions often leading to abnormal maintained postures. In this manuscript, the authors discuss their views on how the cerebellum may play a role in dystonia.

Neural circuits that drive startle behavior, with a focus on the Mauthner cells and spiral fiber neurons of fishes.

Startle behaviors are rapid, high-performance motor responses to threatening stimuli. Startle responses have been identified in a broad range of species across animal diversity. For investigations of neural circuit structure and function, these behaviors offer a number of benefits, including that they are driven by large and identifiable neurons and their neural control is simple in comparison to other behaviors.

Protocols and Hospital Mortality in Critically Ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

Objective: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs.

Design: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week.

Aberrant Purkinje cell activity is the cause of dystonia in a shRNA-based mouse model of Rapid Onset Dystonia-Parkinsonism.

Loss-of-function mutations in the α3 isoform of the sodium pump are responsible for Rapid Onset Dystonia-Parkinsonism (RDP). A pharmacologic model of RDP replicates the most salient features of RDP, and implicates both the cerebellum and basal ganglia in the disorder; dystonia is associated with aberrant cerebellar output, and the parkinsonism-like features are attributable to the basal ganglia. The pharmacologic agent used to generate the model, ouabain, is selective for sodium pumps.

Pros and cons of feeding the septic intensive care unit patient.

Sepsis is a common disease seen in critically ill patients. Many patients with sepsis are unable to provide nutrition for themselves, and therefore initiating artificial nutrition has become part of routine care for these patients. However, studies investigating the optimal route, composition, volume, and duration of nutrition in critically ill patients with sepsis are lacking.

Malignant hypertension with thrombotic microangiopathy and persistent acute kidney injury (AKI).

Two cases of malignant hypertension presenting with acute kidney injury, thrombocytopenia and hemolytic anemia are presented. In both patients a prolonged duration of renal replacement therapy was required. The plasma levels of ADAMTS13 enzyme were not helpful in delineating the precise pathogenesis in both cases, as the decrements were not severe.

Short latency cerebellar modulation of the basal ganglia.

The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time.