Severe Motor Research Articles

Drumming-PD/HD: The impact of a pilot group drumming-based music therapy intervention on people living with Parkinson’s disease and Huntington’s disease and their caregivers

ABSTRACT Introduction Only a few studies have explored the quality of life (QoL) of individuals with Parkinson’s disease (PD) and Huntington’s disease (HD), along with the QoL and burden on their caregivers, in the context of group drumming sessions. Methods Two groups (PD: 6 patients and 6 caregivers; HD: 3 patients and 2 caregivers) attended 60-minute group drumming sessions twice weekly for 12 weeks, choosing instruments based on preference or ability. QoL for all participants, motor severity for PD and HD participants, and caregiver burden levels were collected at baseline, 6, 12, and 18 weeks (follow-up visit). All participants completed an exit questionnaire at 18 weeks. Results PD participants showed motor improvements over 12 and 18 weeks, while their social role satisfaction declined. PD caregivers reported increased social role satisfaction over the same time intervals. HD participants did not show consistent motor changes. PD caregivers’ depression ratings decreased, while PD participants’ depression ratings increased. PD and HD caregivers’ burden increased from baseline to 6 weeks, then decreased by 12 weeks. All participants reported that they enjoyed playing drums. Discussion This pilot study suggests potential benefits of group drumming for individuals with PD, while highlighting differing impacts on caregivers’ social role satisfaction and burden. The dissociation in social satisfaction between PD patients and caregivers merits further investigation to understand potential causes and future implications. Larger studies are needed to confirm these findings and enable meaningful statistical analysis of outcomes for both PD and HD patients and their caregivers.

Подострый склерозирующий панэнцефалит у детей: описание клинических наблюдений

Subacute sclerosing panencephalitis (SSPE) is a rare complication caused by persistent measles infection and characterized by a decline in cognitive functions and severe motor impairments. Since SSPE is considered a potentially fatal complication of acute measles infection and is typically develops in young individuals especially those infected prior to the age of two years old, special attention must be paid to the implementation of vaccination programs that can prevent severe disease. Thus, the purpose of this research was to present the demographic and clinical characteristics of pediatric patients with SSPE in order to enhance its early diagnosis and to raise the pediatricians' awareness of this serious measles complication. In this series of case reports Authors represent the clinical picture, laboratory and instrumental data of six children with SSPE admitted at the Russian Children's Clinical Hospital with the Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia (Moscow, Russia) in Aug. 2022-Aug. 2024. Authors have conducted an analysis of complaints, clinical symptoms, laboratory, neurophysiological and neuroimaging data of 6 patients with SSPE. All patients have undergone cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI) of the brain and video EEG monitoring during both wakefulness and sleep at the time of diagnosis. Currently, there is no specific treatment for SSPE that would either lead to symptom regression or prevent the related disability. Therefore, vaccination remains the only effective means for the SSPE prevention.

Parental attitudes and experiences in pursuing genetic testing for their child's motor speech disorder.

Rare and typically severe motor speech disorders such as childhood apraxia of speech (CAS) and dysarthria affect about 1 in 1000 children. The genetic basis of these speech disorders is well-documented, with approximately 30% of children who undergo genomic testing receiving an explanatory genetic diagnosis. As more children with speech disorders are offered genetic testing, understanding parental views and experiences around genetic testing for their child is critical in providing effective pre- and post-test genetic counselling. This research explored parental attitudes, experiences, and perceived implications of pursuing genetic testing for their child with motor speech disorder. Semi-structured interviews were conducted with 20 parents of children with CAS or dysarthria who had undergone exome sequencing. Eight parents had received a genetic diagnosis for their child and 12 received uninformative genetic test results. Interviews were transcribed verbatim, co-coded, and analysed using reflexive thematic analysis. Parents were highly motivated to pursue genetic testing for their child's speech disorder due to the perceived personal, clinical, social, and financial utility in obtaining a genetic diagnosis. Regardless of testing outcome, parents experienced complex emotional responses in receiving their child's genetic test results. Parents whose child received a genetic diagnosis reported improved access to funding and clinical care; however, they also hoped for ongoing informational, clinical, and peer support in navigating the uncertainty surrounding their child's rare diagnosis. Conversely, parents who received uninformative genetic test results reported finding meaning in this test outcome, and used emotional-focused and problem-focused strategies to cope with their child's continued diagnostic odyssey.

Evaluating the Clinical Applicability of Multifrequency Bioelectrical Impedance Analysis for Nutritional Status Prediction in Hospitalized Persons With Severe Motor and Intellectual Disabilities.

Persons with severe motor and intellectual disabilities (SMID) have difficulty using general nutritional assessments in the elderly and other populations because of their physical characteristics. The purpose of this study was to investigate the clinical utility of body composition, which has been suggested to be related to biochemical tests in persons with SMID. We calculated cutoff values of body composition predicting malnutrition and compared the usage of peripheral parenteral nutrition for the two groups divided by each body composition cutoff value. We also compared body composition at the baseline between nonsurvivors and survivors. Only group comparisons based on skeletal muscle ratio and extracellular water to total body water (ECW/TBW) cutoffs showed significant differences in the usage of peripheral parenteral nutrition. Nonsurvivors had significantly higher ECW/TBW than survivors at the baseline. In persons with SMID, skeletal muscle ratio and ECW/TBW measured using multifrequency bioelectrical impedance were associated with biochemical indices and ill health. Furthermore, ECW/TBW was also associated with mortality, suggesting that ECW/TBW is a significant measure for nutritional assessment in clinical practice.

CSF GPNMB in Parkinson's disease: A potential association with age and microglial activation

Background Recent evidence suggests a link between glycoprotein non-metastatic melanoma protein B (GPNMB) and Parkinson's disease (PD) pathogenesis. Although elevated plasma GPNMB levels associated with disease severity have been reported in PD, cerebrospinal fluid (CSF) alterations remain elusive. Objective To explore CSF GPNMB alterations and its clinical significance in PD. Methods This study enrolled 118 sporadic PD patients and 40 controls. We examined the potential associations between CSF GPNMB levels and the clinical characteristics or biomarkers of neurodegenerative pathogenesis. Results PD patients had higher CSF GPNMB levels than controls ( p = 0.0159). In the PD group, CSF GPNMB levels correlated with age (age at examination: rs = 0.2511, p = 0.0061; age at onset: rs = 0.2800, p = 0.0021) and the severity of motor and cognitive dysfunction (MDS-UPDRS III score: rs = 0.1998, p = 0.0347; Mini-Mental State Examination score: rs = −0.1922, p = 0.0370). After correcting for multiple comparisons, the correlation with age at onset remained significant. CSF GPNMB levels were also positively correlated with CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in both the PD ( rs = 0.3582, p < 0.0001) and control ( rs = 0.4743, p = 0.0023) groups. Furthermore, multiple regression analysis revealed CSF sTREM2 level as the strongest determinant of CSF GPNMB levels in the PD group (t-value = 3.49, p = 0.0007). Conclusions Elevated CSF GPNMB levels, linked with age and microglial activation, may be a valuable marker for understanding the interplay between aging, neuroinflammation, and PD pathology.

Subcortical tau burden correlates with regional brain atrophy and plasma markers in four-repeat tauopathy parkinsonism

Background 18F-florzolotau positron emission tomography (PET) assists in the in vivo diagnosis of progressive supranuclear palsy (PSP). Objective We aimed to investigate the relationship between 18F-florzolotau uptake and clinical severity, structural volume changes, and plasma markers in four-repeat tauopathies. Methods A total of 80 participants were recruited: 35 with PSP (11 with PSP-Richardson syndrome and 24 with PSP non-Richardson syndrome), 9 with corticobasal syndrome (CBS), 10 with Alzheimer's disease (AD), 8 with Parkinson's disease, and 18 controls. All participants underwent 18F-florzolotau PET, brain magnetic resonance imaging (MRI), and plasma biomarker investigation (total and phosphorylated tau [pTau181], neurofilament light chain, and glial fibrillary acidic protein [GFAP]). Results 18F-Florzolotau uptake was significantly higher in the subcortical regions of the pallidum, subthalamic nucleus (STN), midbrain, red nucleus, and raphe nucleus in PSP patients compared to the other groups (all p < 0.01). Subcortical tau tracer retention assisted in distinguishing PSP and CBS from controls (AUC = 0.836, p < 0.001). Tau tracer retention could differentiate PSP and CBS from AD in cortical ( p < 0.001) and subcortical regions ( p = 0.028). The motor severity of PSP positively correlated with tau burden in STN ( p = 0.044) and substantia nigra ( p = 0.035). Tau tracer uptake was associated with cortical volume changes in CBS ( p = 0.031), PSP non-Richardson syndrome ( p = 0.003), and AD ( p = 0.044). Cortical tau retention correlated with plasma levels of GFAP ( p = 0.001) and pTau181 ( p = 0.036). Conclusions Subcortical 18F-Florzolotau uptake assist the diagnosis of 4R tauopathy parkinsonism. Additionally, regional tau burden contributes to structural brain volume changes and correlates with plasma levels of GFAP and pTau181.

Effects of levodopa/carbidopa intestinal gel infusion on autonomic symptoms in advanced Parkinson's disease: a systematic review.

Autonomic failure has a major impact on the quality of life of individuals with Parkinson's disease(PD), especially in advanced stages of the disease. Levodopa/carbidopa intestinal gel (LCIG) infusion is a well-established treatment for advanced PD with severe motor fluctuations and provides substantial benefit in managing some non-motor symptoms (NMS), such as sleep, fatigue, and neuropsychiatric issues. The effect of LCIG on autonomic symptoms is by contrastnot well known. Here we performed a systematic review on the influence of LCIG therapy on autonomic dysfunction in PD individuals. Following the PRISMA guidelines, we systematically searched for studies that included autonomic outcome measures in LCIG-treated PD individuals, limiting the search to articles written in English and published between January 2005 and June 2023. We evaluated improvement, stability, or worsening of gastrointestinal, urinary, and cardiovascular symptoms at six different timepoints according to clinimetric scale changes compared to baseline. Data on autonomic adverse events (AEs) possibly related to LCIG treatment were also collected. Of the 1476 studies identified in the initial search, 16 ultimately met the inclusion criteria and underwent quality assessment and data extraction, with data from 1361 PD patients (18.3months mean follow-up). Thirteen studies reported improvement or stability of gastrointestinal, urinary, and cardiovascular symptoms over the interventional period. One study found a worsening of cardiovascular symptoms and two of urological symptoms. Regarding safety, seven studies reported gastrointestinal (8.4%), urinary (0.5%), and cardiovascular (1.1%) autonomic LCIG-related AEs. LCIG infusion may help toreduce the burden ofautonomic symptoms in advanced PD. Prospective studies specifically addressing the effect of LCIG on autonomic function in advanced PD are warranted.

Acid-sensing ion channel-1 contributes to the failure of myelin sheath regeneration following spinal cord injury by transcellular delivery of PGE2

BackgroundTraumatic injuries to spinal cord lead to severe motor, sensory, and autonomic dysfunction. The accumulation of inhibitory compounds plays a pivotal role in the secondary damage to sparing neural tissue and the failure of axonal regeneration and remyelination. Acid-sensing ion channel-1(ASIC1A) is widely activated following neurotrauma, including spinal cord injury (SCI). However, its role in SCI remains elusive.MethodsThe effects of acidic environment on the differentiation and genes changes of neural stem cells (NSCs) were assessed by immunofluorescence staining and RNA-sequencing analysis, respectively. The expression of ASIC1A and prostaglandin endoperoxide synthase 2 (PTGS2) were detected by western blot and immunofluorescence staining. The concentration of prostaglandin E2 (PGE2) within NSC-derived extracellular vesicles were evaluated by ELISA. Small-interfering RNAs (siRNAs) were used to knock down Asic1a and Ptgs2 expression in NSCs. The myelin sheath regeneration and axonal remyelination in rats and Asic1a-KO mice were assessed by immunofluorescence staining.ResultsFollowing injury to the spinal cord, ASIC1A was found to be colocalized and upregulated in NSCs. ASIC1A activation prevents the differentiation of NSCs into oligodendrocytes by upregulating PTGS2, which leads to increased production and release of PGE2 within extracellular vesicles (EVs). ASIC1A or PTGS2 deficiency in NSCs counters the ASIC1A-related effects on mediating NSC differentiation by reducing PGE2 expression within NSC-derived EVs. Furthermore, intervention in ASIC1A signaling by administration of ASIC1A inhibitors or genetic deletion of ASIC1A demonstrated a pronounced advantage in enhancing myelin sheath regeneration and axonal remyelination.ConclusionsThe activation of ASIC1A prevents NSC differentiation into oligodendrocytes via the transcellular NSC-to-NSC delivery of PGE2, resulting in the failure of myelin sheath regeneration and axonal remyelination following SCI. The inhibition of ASIC1A presents a promising therapeutic strategy for the treatment of SCI.Graphical

Multiple Abnormal Cutaneous Findings in a Patient With Hypomelanosis of Ito Undergoing General Anesthesia

Hypomelanosis of Ito (HI), a neurocutaneous syndrome, is characterized by skin depigmentation and skeletal, muscular, central nervous system, cardiac, and renal manifestations. A wide variety of cutaneous manifestations besides depigmentation have been reported. Herein we describe a 23-year-old woman with HI whose extracutaneous symptoms included severe mental and motor impairment, convulsions, and deformity of the orofacial region. She also had severe obesity, asthma, multiple allergies, and skin hypersensitivity. Although no extracutaneous manifestations were problematic during perioperative management of dental procedures under general anesthesia, erythema developed at 3 time points: during induction, during emergence, and in recovery. We speculated that mechanical stimuli to the skin and administration of multiple drugs likely caused histamine release, leading to the 3 episodes of erythema. Because patients with HI often have hypersensitivity reactions in the skin, both cutaneous and extracutaneous manifestations should be considered in the anesthetic management of patients with HI.

TAT-PPA1 protects against oxidative stress-induced loss of dopaminergic neurons.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain, resulting in severe motor impairments. Inorganic pyrophosphatase 1 (PPA1) plays a key role in various biological processes, and this study introduces a cell-penetrating PPA1 fusion protein (TAT-PPA1) to explore its transduction into cells and brain tissues. TAT-PPA1 effectively penetrates SH-SY5Y cells and the SN region of PD animal models without toxicity, exhibiting protective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-)-induced cell death. TAT-PPA1 revealed an inhibitory influence on the MAPK signaling pathway and MPTP-induced reactive oxygen species (ROS) production. TAT-PPA1 suppresses JNK, AKT, p53, ERK, and p38 phosphorylation, showcasing its multifaceted role in cell survival pathways. In the MPTP-induced PD animal model, TAT-PPA1 prevents dopaminergic cell death and enhances motor function. This study shows that TAT-PPA1 protects against oxidative stress and cell death in neurodegenerative diseases, suggesting potential as a PD treatment.

Interleukin-3 Modulates Macrophage Phagocytic Activity and Promotes Spinal Cord Injury Repair.

Effective clearance of lipid-rich debris by macrophages is critical for neural repair and regeneration after spinal cord injury (SCI). Interleukin-3 (IL-3) has been implicated in programming microglia to cluster and clear pathological aggregates in neurodegenerative disease. Yet, the influence of IL-3 on lipid debris clearance post-SCI is not well characterized. We established a mouse model of spinal cord compression injury to investigate the role of IL-3. Blockage of IL-3 was achieved through intrathecal delivery of an IL-3-neutralizing antibody, while IL-3 activation was augmented via insitu injection of recombinant IL-3 into the lesion site immediately post-SCI. Immunofluorescence staining was performed to determine IL-3 and IL-3Rα sources and distribution, lipid droplet accumulation, neuron preservation, and axon regeneration after SCI. The Basso Mouse Scale (BMS) and footprint analysis were employed to evaluate locomotor function recovery. We found that IL-3 expression was significantly upregulated post-SCI, peaking at 14 days post-injury (dpi) and persisting until 28 dpi. Notably, IL-3 was primarily secreted by astrocytes surrounding the lesion epicenter. Correspondingly, IL-3Rα was predominantly observed in macrophages within the injury core, also elevating at 14 dpi. Neutralization of IL-3 led to increased lipid droplet accumulation, along with markedly widespread of macrophages and decreased neuronal survival, resulting in severe motor deficits compared to controls. Conversely, insitu injection of IL-3 reduced lipid droplet accumulation in macrophages, preserved neurons, promoted axon regeneration, and ultimately contributed to the recovery of motor function after SCI. Our findings shed light on the role of IL-3 in modulating macrophage phagocytic activity and suggest that the IL-3/IL-3Rα pathway may be a potential therapeutic target for enhancing neural repair and functional recovery after SCI.

Predictors of upper limb motor recovery in stroke survivors: a pre–post test study design

ObjectivesThe study aimed to assess the predictors of upper limb motor recovery in stroke survivors.DesignPre–post test study design.SettingConducted in two centres (First Level Hospital and University Teaching Hospital in Lusaka).ParticipantsPatients...

Genetically confirmed Charcot–Marie–Tooth disease type 2A manifesting with postural tremor: a case report

BackgroundCharcot–Marie–Tooth disease is a spectrum of inherited disorders characterized by both motor and sensory manifestations, which include prominent distal muscle weakness, foot deformities (pes cavus and hammer toes), and sensory deficits. Postural tremor as a manifestation of Charcot–Marie–Tooth is seldom present, except in a variant of Charcot–Marie–Tooth subtype 1 (Roussy–Levy syndrome), and its presence often results in a diagnostic dilemma.Case presentationWe present a 34-year-old Eritrean man who came to our hospital with a complaint of tremors of the hands of 6 months duration. Associated with this, he had difficulty walking and weakness of the distal extremities bilaterally, prominently involving the lower limbs. The patient denied a family history of such illness. Physical examination revealed distal muscle weakness (4+/5 on upper limbs, while 3/5 on lower limbs bilaterally), pes cavus deformity, absent ankle reflexes, and mild vibratory sensory loss. We noted a postural tremor that attenuated when the patient assumed an anatomic position. The tremor was limited to the hands. Nerve conduction study of upper and lower limbs showed moderate to severe motor axonal and demyelinating polyneuropathy (axonal > demyelinating), suggestive of mixed axonal and demyelinating hereditary polyneuropathy. Subsequently, genetic testing revealed copy number changes (heterozygous deletion) on the MPZ and MFN2, while the PMP22 gene showed ambiguous copy number changes (decrease) on exons 2 and 3. Tying the clinical, electrophysiologic, and genetic findings, consideration of Charcot–Marie–Tooth subtype 2A with postural tremor was made. Subsequently, the patient was managed with regular physiotherapy and an anxiolytic resulting in minimal symptom improvement.ConclusionThe present case describes a 34-year-old male patient with Charcot–Marie–Tooth subtype 2A presenting with neuropathic postural tremor, which is a rare presentation of a common hereditary polyneuropathy. This case highlights the fact that tremors can be associated with peripheral neuropathy syndromes, and a high index of suspicion is needed to rightly diagnose our patients.

Associations of motor and neuropsychiatric symptoms with comorbidities in prodromal Parkinson's disease.

To investigate the associations between comorbidities and multimorbidity patterns with motor and neuropsychiatric symptoms in patients with Parkinson's disease (PD) in prodromal PD. Multimorbidity is defined as the coexistence of two or more long-term conditions (LTCs) (also known as multiple comorbidities). A total of 921 participants without PD were included in the Parkinson's Progression Markers Initiative (PPMI) database and were categorized according to the LTC count. Participants were evaluated on motor and psychiatric symptoms. Pearson correlation to examine relationship of comorbidities and target symptoms. The baseline population was analyzed using Multiple linear regression model, while mixed effects model was utilized for longitudinal analysis. Fuzzy C-means clustering analysis was conducted to identify comorbidity patterns, followed by multiple linear regression for further analysis. At baseline, a higher LTC count was significantly correlated with more severe motor (MDS-UPDRS I, II, ADL, all P < 0.05) and neuropsychiatric symptoms (QUIP, P < 0.001). Three multimorbidity patterns were identified. Among them, the cardiometabolic multimorbidity pattern (CAR) had the most significant correlation with the aforementioned symptoms. Our longitudinal analysis indicated that an increase in the LTC count was associated with the exacerbation of motor and neuropsychiatric symptoms. Comorbidities were cross-sectionally and longitudinally associated with the motor and neuropsychiatric symptoms of patients with prodromal PD. Among the three multimorbidity patterns, CAR posed the highest threat to the risk of more severe motor and neuropsychiatric symptoms.

Serum neurotransmitter analysis of motor and non-motor symptoms in Parkinson's patients.

Clinical symptoms of Parkinson's disease (PD) are classified into motor and non-motor symptoms. Mental disorders, especially depression, are one of the major non-motor manifestations of PD. However, the underlying mechanisms remain poorly understood. In the present study, 21 neurotransmitters associated with mental disorders were measured in serum samples from patients and controls using the ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. Additionally, five clinical scales-the MDS Unified Parkinson's Disease Rating Scale (UPDRS), the Non-Motor Symptoms Scale (NMSS), the Mini-Mental State Examination (MMSE), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD)-were used to evaluate the severity of both motor and non-motor symptoms in PD patients. Analysis of neurotransmitter metabolism revealed significant changes in the tryptophan (Trp) metabolic pathway in PD patients. Specifically, levels of Trp, kynurenine (KYN), kynurenic acid (KA), nicotinamide (NAM), and 5-methoxyltryptamine (MeOTA) were substantially decreased. Additionally, three other excitation/inhibiting amino acids-glutamic acid (Glu), 4-aminobutyric acid (GABA), and aspartic acid (Asp)-also declined. Moreover, neurotransmitter conversion ratios, such as KA/KYN, nicotinamide/niacin (NAM/NA), 5-hydroxytryptophan/tryptophan (5-HTP/Trp), and quinolinic acid/kynurenic acid (QA/KA), provided more dynamic insights into disrupted neurotransmitter metabolism. Correlation analyses between scale scores and neurotransmitter levels showed that concentrations of xanthurenic acid (XA) and the turnover rate of 3-hydroxykynurenine (3-HK) were negatively correlated with UPDRS scores, while 5-hydroxytryptamine (5-HT) and GABA levels were negatively correlated with non-motor symptoms in PD patients. In summary, this study elucidates, for the first time, the potential association and dynamics between altered neurotransmitter metabolism and the etiology of PD in terms of motor and non-motor functions. These findings offer novel biomarkers and therapeutic targets for the treatment of PD.

Longitudinal analysis of urinary I-FABP in extremely preterm infants that develop necrotizing enterocolitis.

Intestinal fatty acid binding protein (I-FABP) is an intestinal epithelial protein detectable in infants with necrotizing enterocolitis (NEC). The longitudinal behavior of I-FABP following NEC or its association with gastrointestinal or neurodevelopmental outcomes is unknown. In this secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, we compared infants with and without NEC. Urine I-FABP concentrations in matched infants (n = 70) were measured serially using ELISA and compared using paired analysis. In infants with NEC, the associations of I-FABP levels with short-term outcomes and neurodevelopmental outcomes at 22-26 months corrected age were determined using non-parametric analysis. Infants with NEC were more likely to have cholestasis, death or severe neurodevelopmental impairment, cerebral palsy, and lower Bayley-III motor scores. Baseline urinary I-FABP levels were similar between groups. When compared to controls, infants with NEC had urinary I-FABP concentrations that were higher at diagnosis (median 11 vs 2.6 ng/ml, p = 0.006) and lower post-NEC (median 1 vs 5 ng/ml, p = 0.002). Diagnosis I-FABP levels were not associated with gastrointestinal or neurodevelopmental outcomes at 22-26 months corrected age. In extremely preterm infants, urinary I-FABP was elevated at NEC diagnosis and lower post-NEC compared to matched controls. I-FABP levels were not associated with adverse gastrointestinal or neurodevelopmental outcomes. Urinary intestinal fatty acid binding protein (I-FABP) levels are increased at diagnosis of NEC and fall to below baseline after NEC in extremely preterm infants. Urine I-FABP levels at NEC diagnosis are not associated with cholestasis, intestinal stricture or obstruction, need for additional intestinal surgery after NEC, or neurodevelopmental outcomes at 22-26 months corrected age. Urine I-FABP levels may be useful in the diagnosis of NEC. Diagnostic I-FABP levels do not predict short-term gastrointestinal or neurodevelopmental outcomes after NEC.

Patterns of tau, amyloid and synuclein pathology in ageing, Alzheimer's disease and synucleinopathies.

Alzheimer's disease (AD) is neuropathologically defined by deposits of misfolded hyperphosphorylated tau (HP-tau) and β-amyloid. Lewy body (LB) dementia, which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is characterised pathologically by α-synuclein aggregates. HP-tau and β-amyloid can also occur as copathologies in LB dementia, and a diagnosis mixedAD/DLB can be made if present in sufficient quantities. We hypothesised the spread of these abnormal proteins selectively affects vulnerable areas, resulting in pathologic regional covariance that differentially associates with pre-mortem clinical characteristics. Our aims were to map regional quantitative pathology (HP-tau, β-amyloid, α-synuclein) and investigate the spatial distributions from tissue microarray (TMA) post-mortem samples across healthy aging, AD and LB dementia. The study involved 159 clinico-pathologically diagnosed human post-mortem brains (48 controls, 47 AD, 25 DLB, 20 mixedAD/DLB, 19 PDD). The burden of HP-tau, β-amyloid and α-synuclein was quantitatively assessed in cortical and subcortical areas. Principal components (PC) analysis was applied across all cases to determine the pattern nature of HP-tau, β-amyloid and α-synuclein. Further analyses explored the relationships of these pathological patterns with cognitive and symptom variables. Cortical (tauPC1) and temporolimbic (tauPC2) patterns were observed for HP-tau. For β-amyloid, a cortical-subcortical pattern (amylPC1) was identified. For α-synuclein, four patterns emerged: 'posterior temporal - occipital (synPC1)', 'anterior temporal-frontal (synPC2)', 'parieto-cingulate-insula (synPC3)', and 'frontostriatal-amygdala (synPC4)'. Distinct synPC scores were apparent among DLB, mixedAD/DLB and PDD, and may relate to different spreading patterns of α-synuclein pathology. In dementia, cognitive measures correlated with tauPC1, tauPC2 and amylPC1 pattern scores (P≤0.02), whereas such variables did not relate to α-synuclein parameters in these or combined LB dementia cases. Mediation analysis then revealed that in the presence of amylPC1, tauPC1 had a direct effect on global cognition in dementia (n=65, P=0.04), while tauPC1 mediated the relationship between amylPC1 and cognition through the indirect pathway (amylPC1→ tauPC1 → global cognition) (P<0.05). Lastly, in synucleinopathies, synPC1 and synPC4 pattern scores were associated with visual hallucinations and motor impairment, respectively (P=0.02). In conclusion, distinct patterns of α-synuclein pathology were apparent in LB dementia, which could explain some of the disease heterogeneity and differing spreading patterns among these conditions. Visual hallucinations and motor severity were associated with specific α-synuclein topographies in LB dementia that may be important to the clinical phenotype, and could, after necessary testing/validation, be integrated into semi-quantitative routine pathological assessment.

Construction and performance analysis of DC servo system based on operational amplifier

Abstract. The motivation for researching modelling the severe motor system is its frequent use in applications that demand accurate control of position, speed, or force. Examples include robots and CNC machines, extensively employed and advanced in modern manufacturing processes. The application field of this technology is expanding significantly due to the increasing demand for automation in modern times. In order to achieve seamless integration of the system, using Op-Amp as the central element for signal processing and control is crucial. This research aims to determine the methodology for utilising an operational amplifier (Op-Amp) to construct a model for a direct current (DC) servo motor. Additionally, the research aims to develop a control system and do circuit board simulations.The outcome of this research is to implement theoretical principles into a design model, identify the most appropriate system for this model and develop the corresponding circuit board. This study aims to incorporate a control system to regulate server motors, effectively enhancing the automation process.

Diminished sense of agency inhibits paretic upper-limb use in patients with post-stroke motor deficits

Post-stroke motor deficits often disrupt the voluntary control of body movements, leading to abnormal feelings. Among these, alterations in the sense of agency (SoA), the feeling of controlling one’s movement, are notable because SoA facilitates actions. However, whether patients with more severe motor deficits experience poorer SoA and SoA’s clinical impact on motor activity remain unclear. To address these questions, this longitudinal study quantified SoA in 156 post-stroke patients through factor analyses with multiple question items to differentiate SoA from potentially confounding discomfort. Structural equation modeling revealed that SoA decreased significantly with upper-limb motor deficit severity and that reduced SoA correlated significantly with decreased paretic upper-limb use. Notably, this effect persisted after controlling for motor deficit severity, suggesting a direct clinical impact of SoA on motor activity. Further, improvements in SoA were significantly associated with increased upper-limb use in patients with moderate or severe motor deficits, emphasizing the role of SoA in maintaining or increasing paretic upper-limb activity. These findings highlight the importance of rehabilitation treatments that consider patients' subjective experiences, particularly agency attribution.

Can minor trauma cause asymptomatic cervical spinal cord compression leading to severe cervical spinal cord injury in rats?

The study aimed to determine whether asymptomatic rats with cervical spinal cord compression (CSCC) experience more severe cervical spinal cord injury (SCI) compared with rats without CSCC under the same degree of minor trauma. Four weeks after the polyvinyl alcohol-polyacrylamide hydrogel was implanted into the C5 vertebral canal, asymptomatic rats were selected based on locomotor function score. Mild cervical SCI was subsequently established based on CSCC. The motor function, morphology, neuron loss, myelin destruction, nerve cell apoptosis, microglia activation, and neuroinflammation were evaluated after SCI. Under the same injury conditions, rats in the CSCC group exhibited more severe motor dysfunction compared with those without CSCC. Similarly, asymptomatic CSCC rats showed significant damage to spinal cord tissue, neurons, and myelin. Finally, compared with rats without CSCC, asymptomatic CSCC rats experienced increased nerve cell apoptosis, microglial activation, and neuroinflammation following the same SCI. In asymptomatic CSCC rats, the same degree of minor trauma resulted in more severe cervical SCI compared with rats without CSCC. This was evidenced by increased nerve cell apoptosis, microglial activation, neuron death, myelin destruction, and a strong neuroinflammatory response, leading to severe motor dysfunction.