Author: geoplotsadmin

 Parkinson’s Disease: Gene Therapies

Calcium channel blocker

When more than 20 mg of simvastatin, a lipid-lowering agent, are given with amlodipine, the risk of myopathy increases.[40] The FDA issued a warning to limit simvastatin to a maximum dose of 20 mg if taken with amlodipine based on evidence from the SEARCH trial.[41] Giving amlodipine with Viagra increases the risk of hypotension.[7][10 < wiki amlodipine

 

The prion hypothesis suggests that alpha-synuclein aggregates are pathogenic and can spread to neighboring, healthy neurons and seed new aggregates. Some propose that the heterogeneity of PD may stem from different “strains” of alpha-synuclein aggregates and varying anatomical sites of origin

The incidence rate of falls in Parkinson’s patients is approximately 45 to 68%, thrice that of healthy individuals, and half of such falls result in serious secondary injuries. Falls increase morbidity and mortality.[227]Around 90% of those with PD develop hypokinetic dysarthria, which worsens with disease progression and can hinder communication.[228]Additionally, over 80% 

of PD patients develop dysphagia: consequent inhalation of gastric and oropharyngeal secretions can lead to aspiration pneumonia.[229] Aspiration pneumonia is responsible for 70% of deaths in those with PD.[230]

< wiki

 Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system[1] and is characterized by poor articulation of phonemes.[2] It is a condition in which problems effectively occur with the muscles that help produce speech, often making it very difficult to pronounce words

 For instance, English philosopher Thomas Hobbes was diagnosed with “shaking palsy”—assumed to have been Parkinson’s—but continued writing works such as Leviathan.[289][290][291] Adolf Hitler is widely believed to have had Parkinson’s, and the condition may have influenced his decision making.[292][293][294] Mao Zedong was also reported to have died from the disorder.[295]

https://en.wikipedia.org/wiki/Gene_therapy_in_Parkinson%27s_disease

https://en.wikipedia.org/wiki/Cell-based_therapies_for_Parkinson%27s_disease

https://en.wikipedia.org/wiki/Management_of_Parkinson%27s_disease#

https://en.m.wikipedia.org/wiki/Hypernasal_speech

 The new treatments for PD are in clinical trials and most of them are centered on gene therapy. With this, researchers expect to compensate the loss of dopamine or to protect the dopamine neurons from degeneration.[2] The pharmacological and surgical therapies for PD focus on compensating the ganglia dysfunction caused by the degeneration of the dopaminergic neuron from substantia nigra

As the gut microbiome in PD is often disrupted and produces toxic compounds, fecal microbiota transplants might restore a healthy microbiome and alleviate various motor and non-motor symptoms.[300] Neurotrophic factors—peptides that enhance the growth, maturation, and survival of neurons—show modest results but require invasive surgical administration. Viral vectors may represent a more feasible delivery platform.[304] Calcium channel blockers may be restore the calcium imbalance present in Parkinson’s, and are being investigated as a neuroprotective treatment.[305] Other therapies, like deferiprone, may reduce the abnormal accumulation of iron in PD.[305]

The older you get the righter the binary Cartesian vision of body and soul seems. Tied to a dying carcass…  increasingly it seems that the inversecof happening, a dying mind attached to a living carcass ….

Naturally, phenomenology and neuroscience find a convergence of common interests. However, primarily because of ontological disagreements between phenomenology and philosophy of mind, the dialogue between these two disciplines is still a very controversial subject.[9] 

Husserl himself was very critical towards any attempt to “naturalizing” philosophy, and his phenomenology was founded upon a criticism of empiricism, “psychologism“, and “anthropologism” as contradictory standpoints in philosophy and logic.[10][11] The influential critique of the ontological assumptions of computationalist and representationalist cognitive science, as well as artificial intelligence, made by philosopher Hubert Dreyfus has marked new directions for integration of neurosciences with an embodied ontology. 

The work of Dreyfus has influenced cognitive scientists and neuroscientists to study phenomenology and embodied cognitive science and/or enactivism. One such case is neuroscientist Walter Freeman, whose neurodynamical  analysis has a marked Merleau-Pontyian approach.[12]

Wiki Dreyfus <  Knowing-how and knowing-that. Research in psychology and economics has been able to show that Dreyfus’ (and Heidegger’s) speculation about the nature of human problem solving was essentially correct. Daniel Kahnemann and Amos Tversky collected a vast amount of hard evidence that human beings use two very different methods to solve problems, which they named “system 1” and “system 2”. System one, also known as the  adaptive unconscious, is fast, intuitive and unconscious. System 2 is slow, logical and deliberate.

“Walter J. Freeman III”. Nonlinear Dynamics in Psychology. 21/4. 2017

Abstracts-Neurodynamics-Freeman

Unclear Nuclear 

Two poems transposed into verse: Pastis plus Giraffes

Been thinking of Ovid of late

Alles ist mir Treppenwitz. 

It’s liking sinking into your own past, coming to terms with death, unclear

About  

Before someone more than weighs the nuclear

Option

Serpant en fr.  English?

Chaplinesque : this was an unattainable ideal model for me. Anyone else feel the same?

A Defense of Wishy-washy Liberalism

The music in European TV series 

> Falls occur mainly during posture changes, in particular during a half-turn, or while performing activities that require a double task demand (cognitive or motor).11 The more the second task is difficult, the more the balance control is altered and fall risk increased

> Usually, FOG is improved by visual (e.g. marks on the ground) or auditory cueing (rhythmic sounds). Paradoxically, running, cycling or climbing stairs are performed more easily than usual gait. Generally, freezing is defined as an abrupt difficulty in starting or continuing rhythmic and repetitive movements

> A hyperactivation has also been found in PD patients in the cerebellum, a structure known to be crucial for motor coordination and balance control.57 This hyperactivation was interpreted as a strategy of the central nervous system to compensate for the defective function of the basal ganglia and brainstem but could also be causative. Thus, unraveling the role of cerebellar dysfunction in gait and balance deficits in PD may represent a major challenge for the future. 

In a Phase 2 clinical trial, lixisenatide was found to have beneficial effects on Parkinson’s disease progression. This suggests that lixisenatide may have neuroprotective effects in the substantia nigra, potentially slowing down the neurodegeneration associated with Parkinson’s disease.

However, it’s important to note that while these findings are promising, further research and clinical trials are needed to fully understand the effects of lixisenatide on the substantia nigra and its potential as a treatment for Parkinson’s disease. < grok reply  

https://www.nejm.org/doi/

Lixisenatide

Trial of Lixisenatide in Early Parkinson’s Disease

exenatide

Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study

Multisensory mechanisms of gait and balance in Parkinson’s disease: an integrative review

>  the three dominant theoretical angles present in the field (Zhang et al., 2020). 

“ Inverse effectiveness” theories suggest that older adults depend more on multisensory integration for the maintenance of balance because of age-related deterioration in individual sensory modalities. 

“Attentional control deficit” theory attempts to explain the costliness of dual-task on gait and balance stability by suggesting that attentional resources that would otherwise be allocated to multisensory integration are diverted to the dual-task, leading to impairments in balance. 

Lastly, “larger time window of integration” theories suggest that multisensory integration depends on the binding of information within discrete temporal windows. With peripheral sensory deficits, such as those encountered in aging, these timeframes extend. This extension results in an amalgamation of incongruent multisensory information, ultimately disrupting the processing associated with maintaining balance. These theories need not be mutually exclusive, but none of them seem to emphasize the specific roles of individual sensory modalities.

> Most intriguing, this constellation of doorway-related gait impairments emerges early in the progression of PD, being present several years before the diagnosis 

> Failure of visual processing due to attentional misallocation towards the doorway stimulus prevents the acquisition of sufficient evidence about footholds 1.5–2 seconds into the future, which leads to a freezing event.

> Galvanic vestibular stimulation (GVS) is being actively pursued as a non-invasive treatment for postural instability and gait difficulty symptoms in PD

> PD freezers in medication OFF state were also recently shown to exhibit a profound difficulty with balance on unstable support surfaces in association with longer critical time intervals (Roytman et al., 2023)

> Lastly, recent findings demonstrate that suppression of the right hemispheric cortical cholinergic system in PD patients by high anti-cholinergic burden profoundly affects their ability to effectively integrate visual and vestibular cues for balance on an unstable support surface in medication OFF state (Roytman et al., 2023

 

Normal and pathological gait: what we learn from Parkinson’s disease

> However the most impairing gait disruptions are related with balance deficit and FOG episodes that tend to become resistant to levodopa, thus suggesting the involvement of extra-nigral lesions.1

> “Since these gait and balance deficits are resistant to dopaminergic drugs, their occurrence could be related to the development of extra-dopaminergic lesions in PD patients”

Axial symptoms predict mortality in patients with Parkinson disease and subthalamic stimulation

Deep seek

Naturally, phenomenology and neuroscience find a convergence of common interests. However, primarily because of ontological disagreements between phenomenology and philosophy of mind, the dialogue between these two disciplines is still a very controversial subject.[9]

Husserl himself was very critical towards any attempt to “naturalizing” philosophy, and his phenomenology was founded upon a criticism of empiricism, “psychologism“, and “anthropologism” as contradictory standpoints in philosophy and logic.[10][11] The influential critique of the ontological assumptions of computationalist and representationalist cognitive science, as well as artificial intelligence, made by philosopher Hubert Dreyfus has marked new directions for integration of neurosciences with an embodied ontology.

The work of Dreyfus has influenced cognitive scientists and neuroscientists to study phenomenology and embodied cognitive science and/or enactivism. One such case is neuroscientist Walter Freeman, whose neurodynamical analysis has a marked Merleau-Pontyian approach.[12]

Wiki Dreyfus <  Knowing-how and knowing-that. Research in psychology and economics has been able to show that Dreyfus’ (and Heidegger’s) speculation about the nature of human problem solving was essentially correct. Daniel Kahnemann and Amos Tversky collected a vast amount of hard evidence that human beings use two very different methods to solve problems, which they named “system 1” and “system 2”. System one, also known as the  adaptive unconscious, is fast, intuitive and unconscious. System 2 is slow, logical and deliberate.

Parkinson’s disease

Parkinson’s disease

Parkinson’s Disease: Gene Therapies

Calcium channel blocker

When more than 20 mg of simvastatin, a lipid-lowering agent, are given with amlodipine, the risk of myopathy increases.[40] The FDA issued a warning to limit simvastatin to a maximum dose of 20 mg if taken with amlodipine based on evidence from the SEARCH trial.[41] Giving amlodipine with Viagra increases the risk of hypotension.[7][10 < wiki amlodipine

The prion hypothesis suggests that alpha-synuclein aggregates are pathogenic and can spread to neighboring, healthy neurons and seed new aggregates. Some propose that the heterogeneity of PD may stem from different “strains” of alpha-synuclein aggregates and varying anatomical sites of origin

The incidence rate of falls in Parkinson’s patients is approximately 45 to 68%, thrice that of healthy individuals, and half of such falls result in serious secondary injuries. Falls increase morbidity and mortality.[227]Around 90% of those with PD develop hypokinetic dysarthria, which worsens with disease progression and can hinder communication.[228]Additionally, over 80%

of PD patients develop dysphagia: consequent inhalation of gastric and oropharyngeal secretions can lead to aspiration pneumonia.[229] Aspiration pneumonia is responsible for 70% of deaths in those with PD.[230]

< wiki

Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system[1] and is characterized by poor articulation of phonemes.[2] It is a condition in which problems effectively occur with the muscles that help produce speech, often making it very difficult to pronounce words

For instance, English philosopher Thomas Hobbes was diagnosed with “shaking palsy”—assumed to have been Parkinson’s—but continued writing works such as Leviathan.[289][290][291] Adolf Hitler is widely believed to have had Parkinson’s, and the condition may have influenced his decision making.[292][293][294] Mao Zedongwas also reported to have died from the disorder.[295]

https://en.wikipedia.org/wiki/Gene_therapy_in_Parkinson%27s_disease

https://en.wikipedia.org/wiki/Cell-based_therapies_for_Parkinson%27s_disease

https://en.wikipedia.org/wiki/Management_of_Parkinson%27s_disease#

https://en.m.wikipedia.org/wiki/Hypernasal_speech

The new treatments for PD are in clinical trials and most of them are centered on gene therapy. With this, researchers expect to compensate the loss of dopamine or to protect the dopamine neurons from degeneration.[2] The pharmacological and surgical therapies for PD focus on compensating the ganglia dysfunction caused by the degeneration of the dopaminergic neuron from substantia nigra

As the gut microbiome in PD is often disrupted and produces toxic compounds, fecal microbiota transplants might restore a healthy microbiome and alleviate various motor and non-motor symptoms.[300] Neurotrophic factors—peptides that enhance the growth, maturation, and survival of neurons—show modest results but require invasive surgical administration. Viral vectors may represent a more feasible delivery platform.[304] Calcium channel blockers may be restore the calcium imbalance present in Parkinson’s, and are being investigated as a neuroprotective treatment.[305] Other therapies, like deferiprone, may reduce the abnormal accumulation of iron in PD.[305]