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Journal of Clinical Medicine Jun 2024Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods... (Review)
Review
Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods with increased respiratory symptoms, referred to as pulmonary exacerbations. These exacerbations are hard to predict and associated with lung function decline and the loss of quality of life. To optimise treatment and preserve lung function, there is a need for non-invasive and reliable methods of detection. Breath analysis might be such a method. We systematically reviewed the existing literature on breath analysis to detect pulmonary exacerbations in mucociliary clearance disorders. Extracted data included the study design, technique of measurement, definition of an exacerbation, identified compounds and diagnostic accuracy. Out of 244 identified articles, 18 were included in the review. All studies included patients with CF and two also with PCD. Age and the definition of exacerbation differed between the studies. There were five that measured volatile organic compounds (VOCs) in exhaled breath using gas chromatography with mass spectrometry, two using an electronic nose and eleven measured organic compounds in exhaled breath condensate. Most studies showed a significant correlation between pulmonary exacerbations and one or multiple compounds, mainly hydrocarbons and cytokines, but the validation of these results in other studies was lacking. The detection of pulmonary exacerbations by the analysis of compounds in exhaled breath seems possible but is not near clinical application due to major differences in results, study design and the definition of an exacerbation. There is a need for larger studies, with a longitudinal design, international accepted definition of an exacerbation and validation of the results in independent cohorts.
PubMed: 38929901
DOI: 10.3390/jcm13123372 -
Medicina (Kaunas, Lithuania) Jun 2024Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the... (Review)
Review
Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the feasibility and reliability of the video-based examination remains unclear. The aim of this narrative review is to examine which parts of remote neurological assessment are feasible and reliable in movement disorders. Clinical studies have demonstrated that most parts of the video-based neurological examination are feasible, even in the absence of a third party, including stance and gait-if an assistive device is not required-bradykinesia, tremor, dystonia, some ocular mobility parts, coordination, and gross muscle power and sensation assessment. Technical issues (video quality, internet connection, camera placement) might affect bradykinesia and tremor evaluation, especially in mild cases, possibly due to their rhythmic nature. Rigidity, postural instability and deep tendon reflexes cannot be remotely performed unless a trained healthcare professional is present. A modified version of incomplete Unified Parkinson's Disease Rating Scale (UPDRS)-III and a related equation lacking rigidity and pull testing items can reliably predict total UPDRS-III. UPDRS-II, -IV, Timed "Up and Go", and non-motor and quality of life scales can be administered remotely, while the remote Movement Disorder Society (MDS)-UPDRS-III requires further investigation. In conclusion, most parts of neurological examination can be performed virtually in PD, except for rigidity and postural instability, while technical issues might affect the assessment of mild bradykinesia and tremor. The combined use of wearable devices may at least partially compensate for these challenges in the future.
Topics: Humans; Telemedicine; Movement Disorders; Neurologic Examination; Parkinson Disease; Tremor
PubMed: 38929575
DOI: 10.3390/medicina60060958 -
Medicina (Kaunas, Lithuania) May 2024: Currently, no tool exists to predict clinical outcomes in patients with advanced Parkinson's disease (PD) under levodopa-carbidopa intestinal gel (LCIG) treatment. The... (Observational Study)
Observational Study
An Artificial Neural Network Predicts Gender Differences of Motor and Non-Motor Symptoms of Patients with Advanced Parkinson's Disease under Levodopa-Carbidopa Intestinal Gel.
: Currently, no tool exists to predict clinical outcomes in patients with advanced Parkinson's disease (PD) under levodopa-carbidopa intestinal gel (LCIG) treatment. The aim of this study was to develop a novel deep neural network model to predict the clinical outcomes of patients with advanced PD after two years of LCIG therapy. : This was a longitudinal, 24-month observational study of 59 patients with advanced PD in a multicenter registry under LCIG treatment from September 2019 to September 2021, including 43 movement disorder centers. The data set includes 649 measurements of patients, which make an irregular time series, and they are turned into regular time series during the preprocessing phase. Motor status was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (off) and IV. The NMS was assessed by the NMS Questionnaire (NMSQ) and the Geriatric Depression Scale (GDS), the quality of life by PDQ-39, and severity by Hoehn and Yahr (HY). Multivariate linear regression, ARIMA, SARIMA, and Long Short-Term Memory-Recurrent NeuralNetwork (LSTM-RNN) models were used. : LCIG significantly improved dyskinesia duration and quality of life, with men experiencing a 19% and women a 10% greater improvement, respectively. Multivariate linear regression models showed that UPDRS-III decreased by 1.5 and 4.39 units per one-unit increase in the PDQ-39 and UPDRS-IV indexes, respectively. Although the ARIMA-(2,0,2) model is the best one with AIC criterion 101.8 and validation criteria MAE = 0.25, RMSE = 0.59, and RS = 0.49, it failed to predict PD patients' features over a long period of time. Among all the time series models, the LSTM-RNN model predicts these clinical characteristics with the highest accuracy (MAE = 0.057, RMSE = 0.079, RS = 0.0053, mean square error = 0.0069). : The LSTM-RNN model predicts, with the highest accuracy, gender-dependent clinical outcomes in patients with advanced PD after two years of LCIG therapy.
Topics: Humans; Parkinson Disease; Levodopa; Carbidopa; Male; Female; Drug Combinations; Aged; Gels; Middle Aged; Neural Networks, Computer; Longitudinal Studies; Antiparkinson Agents; Sex Factors; Quality of Life; Treatment Outcome; Severity of Illness Index
PubMed: 38929490
DOI: 10.3390/medicina60060873 -
International Journal of Environmental... May 2024With the increased integration of technologies in the healthcare sector, it is important to understand the benefits emerging technologies may play to reduce demands on...
INTRODUCTION
With the increased integration of technologies in the healthcare sector, it is important to understand the benefits emerging technologies may play to reduce demands on the health care system. The Steadiwear antivibration glove shows promise for enhancing the independence in functional abilities for persons with essential tremors and for alleviating the need for support from the health care system. The objective of this study was to examine Registered Nurses' (RN) perceptions of the potential for the Steadiwear antivibration glove to reduce the need for in-person support from community healthcare workers.
METHODS
Eleven RNs, experienced in providing care in rural communities, participated in a semi-structured interview sharing their perspectives towards use of the Steadiwear antivibration glove in community practice settings. Thematic analysis guided by Braun and Clarke was undertaken.
RESULTS
Nurses described the value of this technology to reduce client needs for support for activities of daily living (e.g., dressing, feeding) and independent activities of daily living (e.g., banking, transportation).
CONCLUSIONS
Enhanced access to this technology may reduce the need for nursing and personal care support from the health system. Therefore the Steadiwear antivibration glove also shows potential to delay and/or prevent the need for more intensive support and mitigate the need for transition to a long-term care facility.
Topics: Humans; Rural Population; Qualitative Research; Female; Male; Middle Aged; Adult; Nurses; Tremor; Activities of Daily Living; Home Care Services
PubMed: 38928960
DOI: 10.3390/ijerph21060714 -
Brain Sciences Jun 2024Parkinson's disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical...
Parkinson's disease (PD) is a progressive neurological disorder that is typically characterized by a range of motor dysfunctions, and its impact extends beyond physical abnormalities into emotional well-being and cognitive symptoms. The loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) leads to an array of dysfunctions in the functioning of the basal ganglia (BG) circuitry that manifests into PD. While active research is being carried out to find the root cause of SNc cell death, various therapeutic techniques are used to manage the symptoms of PD. The most common approach in managing the symptoms is replenishing the lost dopamine in the form of taking dopaminergic medications such as levodopa, despite its long-term complications. Another commonly used intervention for PD is deep brain stimulation (DBS). DBS is most commonly used when levodopa medication efficacy is reduced, and, in combination with levodopa medication, it helps reduce the required dosage of medication, prolonging the therapeutic effect. DBS is also a first choice option when motor complications such as dyskinesia emerge as a side effect of medication. Several studies have also reported that though DBS is found to be effective in suppressing severe motor symptoms such as tremors and rigidity, it has an adverse effect on cognitive capabilities. Henceforth, it is important to understand the exact mechanism of DBS in alleviating motor symptoms. A computational model of DBS stimulation for motor symptoms will offer great insights into understanding the mechanisms underlying DBS, and, along this line, in our current study, we modeled a cortico-basal ganglia circuitry of arm reaching, where we simulated healthy control (HC) and PD symptoms as well as the DBS effect on PD tremor and bradykinesia. Our modeling results reveal that PD tremors are more correlated with the theta band, while bradykinesia is more correlated with the beta band of the frequency spectrum of the local field potential (LFP) of the subthalamic nucleus (STN) neurons. With a DBS current of 220 pA, 130 Hz, and a 100 microsecond pulse-width, we could found the maximum therapeutic effect for the pathological dynamics simulated using our model using a set of parameter values. However, the exact DBS characteristics vary from patient to patient, and this can be further studied by exploring the model parameter space. This model can be extended to study different DBS targets and accommodate cognitive dynamics in the future to study the impact of DBS on cognitive symptoms and thereby optimize the parameters to produce optimal performance effects across modalities. Combining DBS with rehabilitation is another frontier where DBS can reduce symptoms such as tremors and rigidity, enabling patients to participate in their therapy. With DBS providing instant relief to patients, a combination of DBS and rehabilitation can enhance neural plasticity. One of the key motivations behind combining DBS with rehabilitation is to expect comparable results in motor performance even with milder DBS currents.
PubMed: 38928620
DOI: 10.3390/brainsci14060620 -
International Journal of Molecular... Jun 2024Coenzyme Q10 (CoQ10) plays a key role in many aspects of cellular metabolism. For CoQ10 to function normally, continual interconversion between its oxidised (ubiquinone)... (Review)
Review
Coenzyme Q10 (CoQ10) plays a key role in many aspects of cellular metabolism. For CoQ10 to function normally, continual interconversion between its oxidised (ubiquinone) and reduced (ubiquinol) forms is required. Given the central importance of this ubiquinone-ubiquinol redox cycle, this article reviews what is currently known about this process and the implications for clinical practice. In mitochondria, ubiquinone is reduced to ubiquinol by Complex I or II, Complex III (the Q cycle) re-oxidises ubiquinol to ubiquinone, and extra-mitochondrial oxidoreductase enzymes participate in the ubiquinone-ubiquinol redox cycle. In clinical terms, the outcome of deficiencies in various components associated with the ubiquinone-ubiquinol redox cycle is reviewed, with a particular focus on the potential clinical benefits of CoQ10 and selenium co-supplementation.
Topics: Ubiquinone; Humans; Oxidation-Reduction; Mitochondria; Animals; Selenium; Ataxia; Muscle Weakness; Mitochondrial Diseases
PubMed: 38928470
DOI: 10.3390/ijms25126765 -
International Journal of Molecular... Jun 2024Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder currently affecting the ageing population. Although the aetiology of PD has yet to be...
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder currently affecting the ageing population. Although the aetiology of PD has yet to be fully elucidated, environmental factors such as exposure to the naturally occurring neurotoxin rotenone has been associated with an increased risk of developing PD. Rotenone inhibits mitochondrial respiratory chain (MRC) complex I activity as well as induces dopaminergic neuronal death. The aim of the present study was to investigate the underlying mechanisms of rotenone-induced mitochondrial dysfunction and oxidative stress in an in vitro SH-SY5Y neuronal cell model of PD and to assess the ability of pre-treatment with Coenzyme Q (CoQ) to ameliorate oxidative stress in this model. Spectrophotometric determination of the mitochondrial enzyme activities and fluorescence probe studies of reactive oxygen species (ROS) production was assessed. Significant inhibition of MRC complex I and II-III activities was observed, together with a significant loss of neuronal viability, CoQ status, and ATP synthesis. Additionally, significant increases were observed in intracellular and mitochondrial ROS production. Remarkably, CoQ supplementation was found to reduce ROS formation. These results have indicated mitochondrial dysfunction and increased oxidative stress in a rotenone-induced neuronal cell model of PD that was ameliorated by CoQ supplementation.
Topics: Ubiquinone; Rotenone; Mitochondria; Humans; Oxidative Stress; Reactive Oxygen Species; Neurons; Parkinson Disease; Cell Line, Tumor; Muscle Weakness; Cell Survival; Electron Transport Complex I; Ataxia; Mitochondrial Diseases
PubMed: 38928331
DOI: 10.3390/ijms25126622 -
International Journal of Molecular... Jun 2024Biotin (vitamin B7, or vitamin H) is a water-soluble B-vitamin that functions as a cofactor for carboxylases, i.e., enzymes involved in the cellular metabolism of fatty... (Review)
Review
Biotin (vitamin B7, or vitamin H) is a water-soluble B-vitamin that functions as a cofactor for carboxylases, i.e., enzymes involved in the cellular metabolism of fatty acids and amino acids and in gluconeogenesis; moreover, as reported, biotin may be involved in gene regulation. Biotin is not synthesized by human cells, but it is found in food and is also produced by intestinal bacteria. Biotin status/homeostasis in human individuals depends on several factors, including efficiency/deficiency of the enzymes involved in biotin recycling within the human organism (biotinidase, holocarboxylase synthetase), and/or effectiveness of intestinal uptake, which is mainly accomplished through the sodium-dependent multivitamin transporter. In the last years, administration of biotin at high/"pharmacological" doses has been proposed to treat specific defects/deficiencies and human disorders, exhibiting mainly neurological and/or dermatological symptoms and including biotinidase deficiency, holocarboxylase synthetase deficiency, and biotin-thiamine-responsive basal ganglia disease. On the other hand, according to warnings of the Food and Drug Administration, USA, high biotin levels can affect clinical biotin-(strept)avidin assays and thus lead to false results during quantification of critical biomarkers. In this review article, recent findings/advancements that may offer new insight in the abovementioned research fields concerning biotin will be presented and briefly discussed.
Topics: Humans; Biotin; Homeostasis; Biotinidase Deficiency; Biotinidase; Holocarboxylase Synthetase Deficiency; Carbon-Nitrogen Ligases; Animals; Ataxia; Basal Ganglia Diseases
PubMed: 38928282
DOI: 10.3390/ijms25126578 -
International Journal of Molecular... Jun 2024Mutations in the gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of...
Mutations in the gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with mutations and broaden the clinical spectrum. We suggest screening for in recessive CMT patients with complex phenotypes of ataxia and spasticity.
Topics: Humans; Male; Charcot-Marie-Tooth Disease; Female; Mutation; Adult; Republic of Korea; Muscle Spasticity; Heterozygote; Cohort Studies; Middle Aged; Magnetic Resonance Imaging; Heat-Shock Proteins; Pedigree; Exome Sequencing; Cerebellar Ataxia; Phenotype; Adolescent; Young Adult
PubMed: 38928084
DOI: 10.3390/ijms25126378 -
Genes Jun 2024Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG expansion on the huntingtin () gene and is characterized by progressive... (Review)
Review
Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG expansion on the huntingtin () gene and is characterized by progressive motor, cognitive, and neuropsychiatric decline. Recently, new genetic factors besides CAG repeats have been implicated in the disease pathogenesis. Most genetic modifiers are involved in DNA repair pathways and, as the cause of the loss of CAA interruption in the gene, they exert their main influence through somatic expansion. However, this mechanism might not be the only driver of HD pathogenesis, and future studies are warranted in this field. The aim of the present review is to dissect the many faces of genetics in HD pathogenesis, from cis- and trans-acting genetic modifiers to RNA toxicity, mitochondrial DNA mutations, and epigenetics factors. Exploring genetic modifiers of HD onset and progression appears crucial to elucidate not only disease pathogenesis, but also to improve disease prediction and prevention, develop biomarkers of disease progression and response to therapies, and recognize new therapeutic opportunities. Since the same genetic mechanisms are also described in other repeat expansion diseases, their implications might encompass the whole spectrum of these disorders.
Topics: Huntington Disease; Humans; Huntingtin Protein; Trinucleotide Repeat Expansion; Animals; Epigenesis, Genetic; DNA, Mitochondrial
PubMed: 38927742
DOI: 10.3390/genes15060807