Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment in schizophrenia: results from the multicenter FACE-SZ cohort.

Aim: The anticholinergic properties of medications are associated with poorer cognitive performance in schizophrenia. Numerous scales have been developed to assess anticholinergic burden and yet, there is no consensus indicating which anticholinergic burden scale is more relevant for patients with schizophrenia. We aimed to identify valid scales for estimating the risk of iatrogenic cognitive impairment in schizophrenia.

Identifying ADHD boys by very-low frequency prefrontal fNIRS fluctuations during a rhythmic mental arithmetic task.

Computer-aided diagnosis of attention-deficit/hyperactivity disorder (ADHD) aims to provide useful adjunctive indicators to support more accurate and cost-effective clinical decisions. Deep- and machine-learning (ML) techniques are increasingly used to identify neuroimaging-based features for objective assessment of ADHD. Despite promising results in diagnostic prediction, substantial barriers still hamper the translation of the research into daily clinic.

Maximal tear secretion evoked by controlled stimulation of corneal sensory nerves in healthy individuals and dry eye subjects.

Purpose: To measure, the tear flow changes evoked in healthy subjects and dry eye disease (DED) patients by controlled sensory stimulation of the eye surface with i-Onion™, a new stimulation device.

Methods: Sensory corneal nerves were stimulated with an instrument (i-Onion™) that ejects puffs of CO gas (99.9%) at 200 ml·min for 3s, delivered 5 mm from the cornea.

Unilateral Corneal Insult Also Alters Sensory Nerve Activity in the Contralateral Eye.

After the unilateral inflammation or nerve lesion of the ocular surface, the ipsilateral corneal sensory nerve activity is activated and sensitized, evoking ocular discomfort, irritation, and pain referred to the affected eye. Nonetheless, some patients with unilateral ocular inflammation, infection, or surgery also reported discomfort and pain in the contralateral eye. We explored the possibility that such altered sensations in the non-affected eye are due to the changes in their corneal sensory nerve activity in the contralateral, not directly affected eye.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

Background: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD).

Pharmacokinetics and Safety of a Bilastine Once-Daily, Preservative-Free, Ophthalmic Formulation.

Introduction: Bilastine is a second-generation H antihistamine indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. On the basis of the demonstrated efficacy and safety of the oral formulation, a new ophthalmic formulation of bilastine was recently developed. Previous preclinical studies had indicated that bilastine is mainly absorbed by the conjunctiva and shows low plasma concentration.

Optical Assessment of Nociceptive TRP Channel Function at the Peripheral Nerve Terminal.

Free nerve endings are key structures in sensory transduction of noxious stimuli. In spite of this, little is known about their functional organization. Transient receptor potential (TRP) channels have emerged as key molecular identities in the sensory transduction of pain-producing stimuli, yet the vast majority of our knowledge about sensory TRP channel function is limited to data obtained from in vitro models which do not necessarily reflect physiological conditions.

Sodium Channel Blockers Modulate Abnormal Activity of Regenerating Nociceptive Corneal Nerves After Surgical Lesion.

Purpose: To test the effect of different sodium channel blockers on the electrical activity of corneal nociceptors in intact and surgically injured corneas.

Methods: In anesthetized guinea pigs, a 4-mm diameter corneal flap was performed in one eye at a midstromal depth using a custom-made microkeratome. At different times after surgery (3 hours to 15 days), the electrical activity of corneal nociceptor fibers was recorded from ciliary nerve filaments in the superfused eye in vitro.

Piezo2 Mediates Low-Threshold Mechanically Evoked Pain in the Cornea.

Mammalian Piezo2 channels are essential for transduction of innocuous mechanical forces by proprioceptors and cutaneous touch receptors. In contrast, mechanical responses of somatosensory nociceptor neurons evoking pain, remain intact or are only partially reduced in Piezo2-deficient mice. In the eye cornea, comparatively low mechanical forces are detected by polymodal and pure mechanosensory trigeminal ganglion neurons.

Comparison of accommodations and interventions for youth with ADHD: A randomized controlled trial.

School psychologists have a variety of evidence-based interventions from which to choose when recommending classroom-based strategies for students with attention deficit hyperactivity disorder (ADHD); however, strategies frequently found on individualized education plans are accommodations designed to remove barriers to learning, which have limited empirical evidence. As such, the purpose of the current study was to compare the efficacy of three interventions (i.e.

Influence of CYP2B6 activity score on the pharmacokinetics and safety of single dose efavirenz in healthy volunteers.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor used as first-line therapy for the treatment of HIV infection. Cytochrome P450 (CYP) CYP2B6 G516T (rs3745274) is a well-known predictor of efavirenz disposition. Dose adjustment based on G516T variant has been shown to be beneficial.

Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers.

Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic-induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics.

Pain, Dryness, and Itch Sensations in Eye Surface Disorders Are Defined By a Balance Between Inflammation and Sensory Nerve Injury.

Patients with corneal and conjunctival disorders report an array of ocular surface symptoms including stinging, foreign body sensation, and itching. The intensity and perceptual quality of these sensations and their duration, from brief intervals to long-term symptoms, also vary. We hypothesize that symptomatic differences across disorders reflect differences in the balance between ocular inflammation and nerve injury, with different conditions resulting from predominant effects of one of these, or a combined effect.

Role of TRPM8 Channels in Altered Cold Sensitivity of Corneal Primary Sensory Neurons Induced by Axonal Damage.

The cornea is extensively innervated by trigeminal ganglion cold thermoreceptor neurons expressing TRPM8 (transient receptor potential cation channel subfamily M member 8). These neurons respond to cooling, hyperosmolarity and wetness of the corneal surface. Surgical injury of corneal nerve fibers alters tear production and often causes dry eye sensation.

Influence of CYP450 Enzymes, CES1, PON1, ABCB1, and P2RY12 Polymorphisms on Clopidogrel Response in Patients Subjected to a Percutaneous Neurointervention.

Purpose: Clopidogrel is a thienopyridine prodrug that inhibits platelet aggregation. It is prescribed to prevent atherothrombotic and thromboembolic events in patients receiving a stent implant in carotid, vertebral, or cranial arteries. The influence of cytochrome P-450 (CYP) 2C19 on the response to clopidogrel has been widely studied; however, the effect of other genes involved in clopidogrel absorption and metabolism has not been established in this cohort of patients.

Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics.

Background: Agomelatine is an agonist of the melatoninergic receptors used for the treatment of depression. Our aim was to evaluate the effect of genetic polymorphisms in metabolising enzymes and the P-glycoprotein transporter on agomelatine pharmacokinetics and pharmacodynamics.

Methods: Twenty-eight healthy volunteers receiving a single 25 mg oral dose of agomelatine, were genotyped for nine polymorphisms in cytochrome P450 enzymes ( CYP1A2, CYP2C9 and CYP2C19) and adenosine triphosphate-binding cassette subfamily B member 1 ( ABCB1), by real-time polymerase chain reaction .

The Immunosuppressant Macrolide Tacrolimus Activates Cold-Sensing TRPM8 Channels.

TRPM8 is a polymodal, nonselective cation channel activated by cold temperature and cooling agents that plays a critical role in the detection of environmental cold. We found that TRPM8 is a pharmacological target of tacrolimus (FK506), a macrolide immunosuppressant with several clinical uses, including the treatment of organ rejection following transplants, treatment of atopic dermatitis, and dry eye disease. Tacrolimus is an inhibitor of the phosphatase calcineurin, an action shared with cyclosporine.

Influence of thiopurine S-methyltransferase polymorphisms in mercaptopurine pharmacokinetics in healthy volunteers.

Mercaptopurine is a drug commonly used in the treatment of different types of cancer, especially acute lymphoblastic leukaemia, and autoimmune diseases such as ulcerative colitis or Crohn's disease and in patients receiving organ transplants. It is metabolized by three cytosolic enzymes. One of them, thiopurine S-methyltransferase (TPMT), is responsible for catalysing the methylation reaction of mercaptopurine to 6-methylmercaptopurine, thus inactivating the drug.

Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics and adverse effects.

Fentanyl is an agonist of the μ-opioid receptor commonly used in the treatment of moderate-severe pain. In order to study whether pharmacogenetics explains some of the variability in the response to fentanyl, several genes related to fentanyl receptors, transporters and metabolic enzymes have been analysed. Thirty-five healthy volunteers (19 men and 16 women) receiving a single 300 μg oral dose of fentanyl were genotyped for 9 polymorphisms in cytochrome P450 (CYP) enzymes (CYP3A4 and CYP3A5), ATP-binding cassette subfamily B member 1 (ABCB1), opioid receptor mu 1 (OPRM1), catechol-O-methyltransferase (COMT) and adrenoceptor beta 2 (ADRB2) by real-time PCR.

Effects of aripiprazole on pupillometric parameters related to pharmacokinetics and pharmacogenetics after single oral administration to healthy subjects.

Background: Pupillometry is used for the detection of autonomic dysfunction related to numerous diseases and drug administration. Genetic variants in cytochrome P450 ( CYP2D6, CYP3A4), dopamine receptor ( DRD2, DRD3), serotonin receptor ( HTR2A, HTR2C) and ATP-binding cassette subfamily B ( ABCB1) genes were previously associated with aripiprazole response.

Aims: Our aim was to evaluate if aripiprazole affects pupil contraction and its relationship with pharmacokinetics and pharmacogenetics.

Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy.

Purpose: To define the characteristics and time course of the morphologic and functional changes experienced by corneal sensory nerves after photorefractive keratectomy (PRK).

Methods: Unilateral corneal excimer laser photoablation was performed in 54 anesthetized 3- to 6-month-old mice; 11 naïve animals served as control. Mice were killed 0, 3, 7, 15, and 30 days after PRK.

Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants.

P-glycoprotein, encoded by ABCB1, is an ATP-dependent drug efflux pump which exports substances outside the cell. Some studies described connections between C3435T polymorphism T allele and lower P-glycoprotein expression; therefore, homozygous T/T could show higher plasma levels. Our aim was to evaluate the effect of C3435T on pharmacokinetics of 4 antipsychotics (olanzapine, quetiapine, risperidone and aripiprazole) and 4 antidepressants (trazodone, sertraline, agomelatine and citalopram).

Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice.

Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline of somatosensory perception. Here, we analyze the changes occurring with aging in trigeminal ganglion (TG), TRPM8-expressing cold thermoreceptor neurons innervating the mouse cornea, which participate in the regulation of basal tearing and blinking and have been implicated in the pathogenesis of dry eye disease (DED). TG cell bodies and axonal branches were examined in a mouse line (TRPM8 -EYFP) expressing a fluorescent reporter.