Antipsychotic Drugs: The Antithesis to Neurorehabilitation in Models of Pre-Clinical Traumatic Brain Injury.

Sixty-nine million traumatic brain injuries (TBIs) are reported worldwide each year, and, of those, close to 3 million occur in the United States. In addition to neurobehavioral and cognitive deficits, TBI induces other maladaptive behaviors, such as agitation and aggression, which must be managed for safe, accurate assessment and effective treatment of the patient. The use of antipsychotic drugs (APDs) in TBI is supported by some expert guidelines, which suggests that they are an important part of the pharmacological armamentarium to be used in the management of agitation.

Dual-Catalytic Enantioselective Allylation of -(Heteroaromatic-methyl)imine Derivatives.

We report the dual-catalytic enantioselective allylic alkylation of 2-(pyridylmethyl)amine-derived ketimines with allylic carbonates. The reaction proceeds under mild reaction conditions to generate α-amino heteroaryl benzylamine stereocenters in good yield and enantioselectivity. Enantioselectivity is achieved through the use of a copper catalyst modified with chiral bisphosphine ligand (2,4)-bis(diphenylphosphino)pentane.

Continuum of care and longitudinal recovery in a 17-year-old athlete with second impact syndrome.

Second impact syndrome (SIS) is an uncommon, but devastating sports-related structural brain injury that results from a second head injury before complete recovery from an initial concussion. The pathophysiology of second impact syndrome is poorly understood, but is hypothesized to involve loss of autoregulation, diffuse cerebral edema, with progression to rapid brain herniation syndromes. Here, we present a case of second impact syndrome in an adolescent high school football player who experienced acute brain herniation and coma.

Milnacipran Ameliorates Executive Function Impairments following Frontal Lobe Traumatic Brain Injury in Male Rats: A Multimodal Behavioral Assessment.

Traumatic brain injuries (TBIs) affect more than 10 million patients annually worldwide, causing long-term cognitive and psychosocial impairments. Frontal lobe TBIs commonly impair executive function, but laboratory models typically focus primarily on spatial learning and declarative memory. We implemented a multi-modal approach for clinically relevant cognitive-behavioral assessments of frontal lobe function in rats with TBI and assessed treatment benefits of the serotonin-norepinephrine reuptake inhibitor, milnacipran (MLN).

Aziridine Opening via a Phenonium Ion Enables Synthesis of Complex Phenethylamine Derivatives.

We report that the treatment of unsymmetrical 2,3-disubstituted aziridines with TiCl yields β-phenethylamine products via the intermediacy of a phenonium ion. Derivatization of the products obtained via this method is demonstrated. Computational analysis of the reaction pathway provides insight into the reaction mechanism, including the selectivity of the phenonium opening.

Homologation of Electron-Rich Benzyl Bromide Derivatives via Diazo C-C Bond Insertion.

The ability to manipulate C-C bonds for selective chemical transformations is challenging and represents a growing area of research. Here, we report a formal insertion of diazo compounds into the "unactivated" C-C bond of benzyl bromide derivatives catalyzed by a simple Lewis acid. The homologation reaction proceeds via the intermediacy of a phenonium ion, and the products contain benzylic quaternary centers and an alkyl bromide amenable to further derivatization.

Psychosocial impairment following mild blast-induced traumatic brain injury in rats.

Traumatic brain injury (TBI) is associated with increased risk for mental health disorders, impacting post-injury quality of life and societal reintegration. TBI is also associated with deficits in psychosocial processing, defined as the cognitive integration of social and emotional behaviors, however little is known about how these deficits manifest and their contributions to post-TBI mental health. In this pre-clinical investigation using rats, a single mild blast TBI (mbTBI) induced impairment of psychosocial processing in the absence of confounding physical polytrauma, post-injury motor deficits, affective abnormalities, or deficits in non-social behavior.

Reagent Control Enables Selective and Regiodivergent Opening of Unsymmetrical Phenonium Ions.

We report the first examples of selective and regiodivergent opening of unsymmetrical phenonium ions with chloride ions. These reactions are enabled by the dual role of SnCl and TiCl as Lewis acids and chloride nucleophiles. Reagent control dictates addition of chloride at either the substituted internal position (SnCl) or unsubstituted terminal position (TiCl) of the phenonium ion.

Acrolein-mediated alpha-synuclein pathology involvement in the early post-injury pathogenesis of mild blast-induced Parkinsonian neurodegeneration.

Survivors of blast-induced traumatic brain injury (bTBI) have increased susceptibility to Parkinson's disease (PD), characterized by α-synuclein aggregation and the progressive degeneration of nigrostriatal dopaminergic neurons. Using an established bTBI rat model, we evaluated the changes of α-synuclein and tyrosine hydroxylase (TH), known hallmarks of PD, and acrolein, a reactive aldehyde and marker of oxidative stress, with the aim of revealing key pathways leading to PD post-bTBI. Indicated in both animal models of PD and TBI, acrolein is likely a point of pathogenic convergence.

Email fraud: The search for psychological predictors of susceptibility.

Decisions that we make about email legitimacy can result in a pernicious threat to security of both individuals and organisations. Yet user response to phishing emails is far from uniform; some respond while others do not. What is the source of this diversity in decision-making? From a psychological perspective, we consider cognitive and situational influences that might explain why certain users are more susceptible than others.

Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates.

A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand.

Cognition based bTBI mechanistic criteria; a tool for preventive and therapeutic innovations.

Blast-induced traumatic brain injury has been associated with neurodegenerative and neuropsychiatric disorders. To date, although damage due to oxidative stress appears to be important, the specific mechanistic causes of such disorders remain elusive. Here, to determine the mechanical variables governing the tissue damage eventually cascading into cognitive deficits, we performed a study on the mechanics of rat brain under blast conditions.

Systemic Acrolein Elevations in Mice With Experimental Autoimmune Encephalomyelitis and Patients With Multiple Sclerosis.

Demyelination and axonal injury are the key pathological processes in multiple sclerosis (MS), driven by inflammation and oxidative stress. Acrolein, a byproduct and instigator of oxidative stress, has been demonstrated as a neurotoxin in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, due to the invasive nature of acrolein detection using immunoblotting techniques, the investigation of acrolein in MS has been limited to animal models.

Recent developments in the use of aza-Heck cyclizations for the synthesis of chiral N-heterocycles.

Aza-Heck cyclizations are an emerging method for the construction of chiral N-heterocyclic systems. In these processes, an activated N-O bond replaces the C-X bond (X = halide, OTf) used in conventional Heck reactions, with the associated aza-Pd(ii)-intermediate engaging pendant alkenes in a Heck-like manner. This perspective article commences with an historical overview of the area, which stems from Narasaka's seminal studies using oxime esters as the initiating motif.

Enantioselective Narasaka-Heck cyclizations: synthesis of tetrasubstituted nitrogen-bearing stereocenters.

The first examples of highly enantioselective Narasaka-Heck cyclizations are described. A SPINOL-derived P,N-ligand system enables Pd-catalyzed 5- cyclization of a range of oxime esters with sterically diverse trisubstituted alkenes to generate dihydropyrroles containing tetrasubstituted nitrogen-bearing stereocenters in 56 to 86% yield and 90 : 10 to 95 : 5 e.r.

Differences in postinjury auditory system pathophysiology after mild blast and nonblast acute acoustic trauma.

Hearing difficulties are the most commonly reported disabilities among veterans. Blast exposures during explosive events likely play a role, given their propensity to directly damage both peripheral (PAS) and central auditory system (CAS) components. Postblast PAS pathophysiology has been well documented in both clinical case reports and laboratory investigations.

Palladium-Catalyzed Enantioselective Intermolecular Coupling of Phenols and Allylic Alcohols.

An enantioselective intermolecular coupling of oxygen nucleophiles and allylic alcohols to give β-aryloxycarbonyl compounds is disclosed using a chiral pyridine oxazoline-ligated palladium catalyst under mild conditions. As opposed to the formation of traditional Wacker-type products, enantioselective migratory insertion is followed by β-hydride elimination toward the adjacent alcohol. Deuterium labeling experiments suggest a syn-migratory insertion of the alkene into the Pd-O bond.

Dichotomous mechanistic behavior in Narasaka-Heck cyclizations: electron rich Pd-catalysts generate iminyl radicals.

Pd-catalyzed cyclizations of oxime esters with pendant alkenes are subject to an unusual ligand controlled mechanistic divergence. Pd-systems modified with electron deficient phosphines ( P(3,5-(CF)CH)) promote efficient aza-Heck cyclization, wherein C-N bond formation occurs alkene imino-palladation. Conversely, electron rich ligands, such as P(-Bu), cause deviation to a SET pathway and, in these cases, C-N bond formation occurs cyclization of an iminyl radical.

Is the era of intravenous proton pump inhibitors coming to an end in patients with bleeding peptic ulcers? Meta-analysis of the published literature.

Aims: Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in patients with bleeding peptic ulcers.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding.

Structural and biochemical abnormalities in the absence of acute deficits in mild primary blast-induced head trauma.

Objective: Blast-induced neurotrauma (BINT), if not fatal, is nonetheless potentially crippling. It can produce a wide array of acute symptoms in moderate-to-severe exposures, but mild BINT (mBINT) is characterized by the distinct absence of acute clinical abnormalities. The lack of observable indications for mBINT is particularly alarming, as these injuries have been linked to severe long-term psychiatric and degenerative neurological dysfunction.

Palladium catalyzed cyclizations of oxime esters with 1,2-disubstituted alkenes: synthesis of dihydropyrroles.

Pd-catalyzed cyclizations of oxime esters with 1,2-dialkylated alkenes provide an entry to chiral dihydropyrroles. Substrate and catalyst controlled strategies for selective product formation (vs alternative pyrroles) are outlined.

Substituted pyrroles via olefin cross-metathesis.

Olefin cross-metathesis (CM) provides a short and convenient entry to diverse trans-γ-aminoenones. When exposed to either acid or Heck arylation conditions, these intermediates are converted to mono-, di-, or trisubstituted pyrroles. The value of this chemistry is demonstrated by its application to the tetrasubstituted pyrrole subunit of Atorvastatin.