Discovery of Cilnidipine Cocrystals with Enhanced Dissolution by the Use of Computational Tools and Semiautomatic High-Throughput Screening.

Cocrystals are an attractive option for overcoming drug limitations, such as a low dissolution rate and absorption of poorly water-soluble compounds. Nevertheless, the discovery of new cocrystals remains a trial-and-error approach in which hundreds of coformers and several experimental methods are often tested. To streamline the cocrystal screening, computational methods can be used to select the coformers most likely to form a cocrystal, while high-throughput screening (HTS) approaches can rapidly screen them experimentally.

Will adaptive deep brain stimulation for Parkinson's disease become a real option soon? A Delphi consensus study.

While conventional deep brain stimulation (cDBS) treatment delivers continuous electrical stimuli, new adaptive DBS (aDBS) technology provides dynamic symptom-related stimulation. Research data are promising, and devices are already available, but are we ready for it? We asked leading DBS experts worldwide (n = 21) to discuss a research agenda for aDBS research in the near future to allow full adoption. A 5-point Likert scale questionnaire, along with a Delphi method, was employed.

The "Cocombola Study": A Physical Phantom Model for tDCS-Induced Electric Field Distribution.

Background: Transcranial direct current stimulation (tDCS)-induced electric fields (EFs) acting on brain tissues are hardly controllable. Among physical models used in neuroscience research, watermelons are known as head-like phantoms for their dielectric properties. In this study, we aimed to define an inexpensive and reliable method to qualitatively define the spatial distribution of tDCS-induced EFs based on the use of watermelons.

Is physical therapy recommended for people with parkinson's disease treated with subthalamic deep brain stimulation? a delphi consensus study.

Background: Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson's disease (PwPD), its effect on motor axial symptoms (e.g., postural instability, trunk posture alterations) and gait impairments (e.

Lessons on neurodegeneration and aging from the Lagoon of Venice: the marine invertebrate .

In this work, the authors proposed a novel and interesting animal model for studying human neurodegenerative diseases, , a small invertebrate inhabiting temperate seas worldwide, which shares remarkable similarities with mammals in the expression of genes involved in pathological aging.

'Knock down the brain': a nonlinear analysis of electroencephalography to study the effects of sub-concussion in boxers.

Background And Purpose: Boxing is associated with a high risk of head injuries and increases the likelihood of chronic traumatic encephalopathy. This study explores the effects of sub-concussive impacts on boxers by applying both linear and nonlinear analysis methods to electroencephalogram (EEG) data.

Methods: Twenty-one boxers were selected (mean ± SD, age 28.

Asymmetries of the subthalamic activity in Parkinson's disease: phase-amplitude coupling among local field potentials.

The role of brain asymmetries of dopaminergic neurons in motor symptoms of Parkinson's disease is still undefined. Local field recordings from the subthalamic nucleus revealed some neurophysiological biomarkers of the disease: increased beta activity, increased low-frequency activity and high-frequency oscillations. Phase-amplitude coupling coordinates the timing of neuronal activity and allows determining the mechanism for communication within distinct regions of the brain.

Cognitive trajectories after surgery: Guideline hints for assessment and treatment.

Elderly patients who undergo major surgery (not-neurosurgical) under general anaesthesia frequently complain about cognitive difficulties, especially during the first weeks after surgical "trauma". Although recovery usually occurs within a month, about one out of four patients develops full-blown postoperative Neurocognitive disorders (NCD) which compromise quality of life or daily autonomy. Mild/Major NCD affect approximately 10% of patients from three months to one year after major surgery.

Water-mediated phase transformations of posaconazole: An intricate jungle of crystal forms.

Posaconazole is a broad-spectrum antifungal agent exhibiting rich polymorphism. Up to now, a total of fourteen different crystal forms have been reported, sometimes with an ambiguous nomenclature, but less is known about their properties and stability relationships. Investigating the solid-state of a drug compound is essential to identify the most stable form under working conditions and to prevent the risk of undesired solid-phase transformations under processing and storage.

Shock waves modulate corticospinal excitability: A proof of concept for further rehabilitation purposes?

Background: Focal extracorporeal shock wave therapy (fESWT) is a physical therapy vastly studied and used for various musculoskeletal disorders. However, the effect of fESWT on central nervous system is still to be determined.

Objective: To elucidate spinal and supra-spinal mechanisms of fESWT in healthy subjects, in order to widen the spectrum of its clinical applications.

Monopolar tDCS might affect brainstem reflexes: A computational and neurophysiological study.

Objective: To assess whether monopolar multi-electrode transcranial direct current stimulation (tDCS) montages might selectively affect deep brain structures through computational predictions and neurophysiological assessment.

Methods: Electric field distribution in deep brain structures (i.e.

Leveraging the use of in vitro and computational methods to support the development of enabling oral drug products: An InPharma commentary.

Due to the strong tendency towards poorly soluble drugs in modern development pipelines, enabling drug formulations such as amorphous solid dispersions, cyclodextrins, co-crystals and lipid-based formulations are frequently applied to solubilize or generate supersaturation in gastrointestinal fluids, thus enhancing oral drug absorption. Although many innovative in vitro and in silico tools have been introduced in recent years to aid development of enabling formulations, significant knowledge gaps still exist with respect to how best to implement them. As a result, the development strategy for enabling formulations varies considerably within the industry and many elements of empiricism remain.

Modeling Electric Fields in Transcutaneous Spinal Direct Current Stimulation: A Clinical Perspective.

Clinical findings suggest that transcutaneous spinal direct current stimulation (tsDCS) can modulate ascending sensitive, descending corticospinal, and segmental pathways in the spinal cord (SC). However, several aspects of the stimulation have not been completely understood, and realistic computational models based on MRI are the gold standard to predict the interaction between tsDCS-induced electric fields and anatomy. Here, we review the electric fields distribution in the SC during tsDCS as predicted by MRI-based realistic models, compare such knowledge with clinical findings, and define the role of computational knowledge in optimizing tsDCS protocols.

Multiple Forms of Neural Cell Death in the Cyclical Brain Degeneration of A Colonial Chordate.

Human neuronal loss occurs through different cellular mechanisms, mainly studied in vitro. Here, we characterized neuronal death in , a marine colonial tunicate that shares substantial genomic homology with mammals and has a life history in which controlled neurodegeneration happens simultaneously in the brains of adult zooids during a cyclical phase named takeover. Using an ultrastructural and transcriptomic approach, we described neuronal death forms in adult zooids before and during the takeover phase while comparing adult zooids in takeover with their buds where brains are refining their structure.

The Effects of a New Integrated and Multidisciplinary Cognitive Rehabilitation Program Based on Mindfulness and Reminiscence Therapy in Patients with Parkinson's Disease and Mild Cognitive Impairment: A Pilot Study.

: Mindfulness trainings have shown promising results as treatment for behavioural symptoms in several pathologies. In addition, mindfulness protocols induced an improvement in memory and attention. Therefore, mindfulness could be an effective intervention for patients affected by Parkinson's disease (PD) and mild cognitive impairment (MCI), who are characterized by both behavioural and cognitive dysfunctions.

Relationship between Reaction Times and Post-COVID-19 Symptoms Assessed by a Web-Based Visual Detection Task.

Long-COVID is a clinical condition in which patients affected by SARS-CoV-2 usually report a wide range of physical and cognitive symptoms from 3 to 6 months after the infection recovery. The aim of the current study was to assess the link between self-reported long-COVID symptoms and reaction times (RTs) in a self-administered Visual Detection Task (VDT) in order to identify the predictor symptoms of the slowing in reaction times to determine attention impairment. In total, 362 participants (age (mean ± S.

Exploring the Cocrystal Landscape of Posaconazole by Combining High-Throughput Screening Experimentation with Computational Chemistry.

The development of multicomponent crystal forms, such as cocrystals, represents a means to enhance the dissolution and absorption properties of poorly water-soluble drug compounds. However, the successful discovery of new pharmaceutical cocrystals remains a time- and resource-consuming process. This study proposes the use of a combined computational-experimental high-throughput approach as a tool to accelerate and improve the efficiency of cocrystal screening exemplified by posaconazole.

Not myopathic, but autonomic changes in patients with long-COVID syndrome: a case series.

Introduction: Neurological sequelae following SARS-CoV-2 infection still represent a serious concern both for neurologists and neuroscientists. In our paper, we investigated pain, myalgia, and fatigue as symptoms in long-COVID patients with an electrophysiological approach, comprising the evaluation of sympathetic skin responses (SSRs) and quantitative electromyography (qEMG).

Materials And Methods: Twelve patients were enrolled (mean age, 47.

Neuroprotection and Non-Invasive Brain Stimulation: Facts or Fiction?

Non-Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and repetitive Magnetic Transcranial Stimulation (rTMS), are well-known non-pharmacological approaches to improve both motor and non-motor symptoms in patients with neurodegenerative disorders. Their use is of particular interest especially for the treatment of cognitive impairment in Alzheimer's Disease (AD), as well as axial disturbances in Parkinson's (PD), where conventional pharmacological therapies show very mild and short-lasting effects. However, their ability to interfere with disease progression over time is not well understood; recent evidence suggests that NIBS may have a neuroprotective effect, thus slowing disease progression and modulating the aggregation state of pathological proteins.

Electric Fields Induced in the Brain by Transcranial Electric Stimulation: A Review of In Vivo Recordings.

Transcranial electrical stimulation (tES) techniques, such as direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), cause neurophysiological and behavioral modifications as responses to the electric field are induced in the brain. Estimations of such electric fields are based mainly on computational studies, and in vivo measurements have been used to expand the current knowledge. Here, we review the current tDCS- and tACS-induced electric fields estimations as they are recorded in humans and non-human primates using intracerebral electrodes.

Cerebellar tDCS as Therapy for Cerebellar Ataxias.

In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques to influence cerebellar activity and the effects of cerebellar stimulation on other brain regions through its multiple complex projections. From the early 1990s, with the discovery of the so-called cerebellar inhibition (CBI), several studies have focused their attention on the use of cerebellar NIBS as treatment for different motor disorders. Cerebellar ataxias (CAs) represent the prototypical clinical manifestation of cerebellar alterations, but other movement disorders, such as Parkinson's disease, essential tremor, and dystonia have also been associated with alterations of networks which include the cerebellum, or of the cerebellum itself.

Consensus Paper: Novel Directions and Next Steps of Non-invasive Brain Stimulation of the Cerebellum in Health and Disease.

The cerebellum is involved in multiple closed-loops circuitry which connect the cerebellar modules with the motor cortex, prefrontal, temporal, and parietal cortical areas, and contribute to motor control, cognitive processes, emotional processing, and behavior. Among them, the cerebello-thalamo-cortical pathway represents the anatomical substratum of cerebellum-motor cortex inhibition (CBI). However, the cerebellum is also connected with basal ganglia by disynaptic pathways, and cerebellar involvement in disorders commonly associated with basal ganglia dysfunction (e.

Deep brain stimulation: is it time to change gears by closing the loop?

Adaptive deep brain stimulation (aDBS) is a form of invasive stimulation that was conceived to overcome the technical limitations of traditional DBS, which delivers continuous stimulation of the target structure without considering patients' symptoms or status in real-time. Instead, aDBS delivers on-demand, contingency-based stimulation. So far, aDBS has been tested in several neurological conditions, and will be soon extensively studied to translate it into clinical practice.

Effects of Transcutaneous Spinal Direct Current Stimulation (tsDCS) in Patients With Chronic Pain: A Clinical and Neurophysiological Study.

Chronic pain is a complex clinical condition, often devastating for patients and unmanageable with pharmacological treatments. Converging evidence suggests that transcutaneous spinal Direct Current Stimulation (tsDCS) might represent a complementary therapy in managing chronic pain. In this randomized, double-blind and sham-controlled crossover study, we assessed tsDCS effects in chronic pain patients.

Adaptive deep brain stimulation (aDBS).

Deep brain stimulation is an established technique for the treatment of movement disorders related to neurodegenerative diseases such as Parkinson's disease (PD) and essential tremor (ET). Its application seems also feasible for the treatment of neuropsychiatric disorders such as treatment resistant depression (TRD) and Tourette's syndrome (TS). In a typical deep brain stimulation system, the amount of current delivered to the patients is constant and regulated by the physician.