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Frontiers in Physiology 2022Parkinson's disease (PD) is a progressive neurological disorder characterized by movement disorders, such as gait instability. This study investigated whether certain...
Parkinson's disease (PD) is a progressive neurological disorder characterized by movement disorders, such as gait instability. This study investigated whether certain spatial features of foot trajectory are characteristic of patients with PD. The foot trajectory of patients with mild and advanced PD in on-state and healthy older and young individuals was estimated from acceleration and angular velocity measured by inertial measurement units placed on the subject's shanks, just above the ankles. We selected six spatial variables in the foot trajectory: forward and vertical displacements from heel strike to toe-off, maximum clearance, and change in supporting leg (F1 to F3 and V1 to V3, respectively). Healthy young individuals had the greatest F2 and F3 values, followed by healthy older individuals, and then mild PD patients. Conversely, the vertical displacements of mild PD patients were larger than the healthy older individuals. Still, those of healthy older individuals were smaller than the healthy young individuals except for V3. All six displacements of the advanced PD patients were smaller than the mild PD patients. To investigate features in foot trajectories in detail, a principal components analysis and soft-margin kernel support vector machine was used in machine learning. The accuracy in distinguishing between mild PD patients and healthy older individuals and between mild and advanced PD patients was 96.3 and 84.2%, respectively. The vertical and forward displacements in the foot trajectory was the main contributor. These results reveal that large vertical displacements and small forward ones characterize mild and advanced PD patients, respectively.
PubMed: 35600314
DOI: 10.3389/fphys.2022.726677 -
Neural Regeneration Research Jul 2024Patients with mild traumatic brain injury have a diverse clinical presentation, and the underlying pathophysiology remains poorly understood. Magnetic resonance imaging...
Patients with mild traumatic brain injury have a diverse clinical presentation, and the underlying pathophysiology remains poorly understood. Magnetic resonance imaging is a non-invasive technique that has been widely utilized to investigate neurobiological markers after mild traumatic brain injury. This approach has emerged as a promising tool for investigating the pathogenesis of mild traumatic brain injury. Graph theory is a quantitative method of analyzing complex networks that has been widely used to study changes in brain structure and function. However, most previous mild traumatic brain injury studies using graph theory have focused on specific populations, with limited exploration of simultaneous abnormalities in structural and functional connectivity. Given that mild traumatic brain injury is the most common type of traumatic brain injury encountered in clinical practice, further investigation of the patient characteristics and evolution of structural and functional connectivity is critical. In the present study, we explored whether abnormal structural and functional connectivity in the acute phase could serve as indicators of longitudinal changes in imaging data and cognitive function in patients with mild traumatic brain injury. In this longitudinal study, we enrolled 46 patients with mild traumatic brain injury who were assessed within 2 weeks of injury, as well as 36 healthy controls. Resting-state functional magnetic resonance imaging and diffusion-weighted imaging data were acquired for graph theoretical network analysis. In the acute phase, patients with mild traumatic brain injury demonstrated reduced structural connectivity in the dorsal attention network. More than 3 months of follow-up data revealed signs of recovery in structural and functional connectivity, as well as cognitive function, in 22 out of the 46 patients. Furthermore, better cognitive function was associated with more efficient networks. Finally, our data indicated that small-worldness in the acute stage could serve as a predictor of longitudinal changes in connectivity in patients with mild traumatic brain injury. These findings highlight the importance of integrating structural and functional connectivity in understanding the occurrence and evolution of mild traumatic brain injury. Additionally, exploratory analysis based on subnetworks could serve a predictive function in the prognosis of patients with mild traumatic brain injury.
PubMed: 38051899
DOI: 10.4103/1673-5374.387971 -
Oxidative Medicine and Cellular... 2022Cerebral infarct penumbra due to hypoxia and toxin accumulation is not conducive to the transplantation of neural stem cells (NSCs), although mild hypothermia can...
Cerebral infarct penumbra due to hypoxia and toxin accumulation is not conducive to the transplantation of neural stem cells (NSCs), although mild hypothermia can improve the local microenvironment of the ischemic penumbra and exert neuroprotective effects. However, insufficient understanding of the molecular mechanism by which mild hypothermia protects the brain limits widespread clinical application. This study evaluated the molecular mechanism of mild hypothermia-induced brain protection from the perspective of global protein small ubiquitin-like modifier (SUMO) modification, with the aim of improving NSC transplant survival rates in the penumbra to enhance neurological function. NSCs from neonatal rats were extracted to detect the effects of hypoxia and mild hypothermia on SUMOylation modification levels, cell stemness, and hypoxia-induced injury. Overexpression and knockdown of UBC9 in NSCs were used to evaluate their ability to maintain stemness and withstand hypoxic injury. Finally, a rat middle cerebral artery occlusion (MCAO) model was used to verify the effect of mild hypothermia treatment and UBC9 overexpression on neural function of NSCs following penumbra transplantation in rats. Results showed that hypoxia and mild hypothermia promoted both the SUMOylation modification and maintenance of NSC stemness. Overexpression of UBC9 enhanced the abilities of NSCs to maintain stemness and resist hypoxic injury, while UBC9 knockdown had the opposite effect. Following transplantation into the ischemic penumbra of MCAO model rats, mild hypothermia and -overexpressing NSCs significantly reduced cerebral infarct areas and improved neurological function. In conclusion, this study demonstrated that global protein SUMOylation is an important molecular mechanism for NSCs to tolerate hypoxia, and mild hypothermia can further increase the degree of global SUMOylation to enhance the hypoxia tolerance of NSCs, which increases their survival during transplantation in situ and ability to perform nerve repair in the penumbra of cerebral infarction.
Topics: Animals; Hypothermia; Hypoxia; Infarction, Middle Cerebral Artery; Neural Stem Cells; Rats; Sumoylation
PubMed: 35669854
DOI: 10.1155/2022/6503504 -
Geriatrics & Gerontology International Feb 2021This study aimed to assess whether CogEvo, a computerized cognitive assessment and training tool, could distinguish patients with mild Alzheimer's disease and mild...
Usefulness of CogEvo, a computerized cognitive assessment and training tool, for distinguishing patients with mild Alzheimer's disease and mild cognitive impairment from cognitively normal older people.
AIM
This study aimed to assess whether CogEvo, a computerized cognitive assessment and training tool, could distinguish patients with mild Alzheimer's disease and mild cognitive impairment from cognitively normal older people.
METHODS
This cross-sectional study enrolled 166 participants with Alzheimer's disease, mild cognitive impairment and cognitively normal older people. In CogEvo, five types of cognitive tasks were carried out, and the z-scores were used as a composite score. Logistic regression and receiver operating characteristics analyses were then carried out to evaluate the usefulness of CogEvo in distinguishing between the three groups.
RESULTS
CogEvo and Mini-Mental State Examination scores showed excellent correlation, and could significantly differentiate between the Alzheimer's disease, mild cognitive impairment and cognitively normal older people groups (Mini-Mental State Examination 20.4 ± 3.5, 25.5 ± 1.6 and 27.6 ± 2.0, respectively; CogEvo: -1.9 ± 0.9, -0.8 ± 0.8 and 0.0 ± 1.0, respectively; both P < 0.001 by analysis of variance). Logistic regression analysis adjusted for age, sex and years of education significantly differentiated the mild cognitive dysfunction group (mild cognitive impairment plus mild Alzheimer's disease; n = 78) from the cognitively normal group (n = 88) (P < 0.001), whereas receiver operating characteristics analysis showed moderate accuracy (area under the receiver operating characteristic curve 0.830).
CONCLUSIONS
These results suggest that CogEvo, a computerized cognitive assessment tool, is useful for evaluating early-stage cognitive impairment. Further studies are required to assess its effectiveness as a combination assessment and training tool. Geriatr Gerontol Int 2021; 21: 192-196.
Topics: Aged; Alzheimer Disease; Cognition; Cognitive Dysfunction; Cross-Sectional Studies; Humans; Mental Status and Dementia Tests
PubMed: 33336432
DOI: 10.1111/ggi.14110 -
Journal of Clinical Medicine Oct 2022To evaluate the efficacy of biofeedback and electrical stimulation-assisted pelvic floor muscle training (PFMT) between women with mild and moderate to severe stress...
BACKGROUND
To evaluate the efficacy of biofeedback and electrical stimulation-assisted pelvic floor muscle training (PFMT) between women with mild and moderate to severe stress urinary incontinence (SUI).
METHODS
This retrospective cohort study was conducted at a single center from 2014 to 2021. We included 57 patients with urodynamically proven SUI who underwent a biofeedback and electrical stimulation-assisted PFMT. They were categorized into mild and moderate to severe SUI. One-hour pad test from 2 to 10 g was defined as mild SUI, and ≥11 g was defined as moderate to severe SUI.
RESULTS
Fifty-seven patients were reviewed during the study period. Incontinence-related symptoms of distress, including the UDI-6, ISI, and VAS, all significantly improved in the mild SUI group ( = 0.001, = 0.001 and = 0.010, respectively), while only UDI-6 and VAS statistically improved in the moderate to severe SUI group ( = 0.027 and = 0.010, respectively). There was significant improvement in IIQ-7 in the mild SUI group during serial treatments, but only in Session 6 in the moderate to severe SUI group. After 18 sessions of treatment, the UDI-6, ISI, and IIQ-7 scores showed significantly greater improvements in the mild SUI group compared to the moderate to severe SUI group ( = 0.003, = 0.025, and = 0.002, respectively).
CONCLUSIONS
Although biofeedback and electrical stimulation-assisted PFMT is an effective treatment option for SUI, it is more beneficial for patients with mild SUI and a 1-h pad weight ≤ 10 g urine leak.
PubMed: 36362651
DOI: 10.3390/jcm11216424 -
Frontiers in Psychiatry 2020Recent psychoneuroimmunology research has provided new insight into the etiology and pathogenesis of severe mental disorders (SMDs). The mild encephalitis (ME)... (Review)
Review
Recent psychoneuroimmunology research has provided new insight into the etiology and pathogenesis of severe mental disorders (SMDs). The mild encephalitis (ME) hypothesis was developed with the example of human Borna disease virus infection years ago and proposed, that a subgroup SMD patients, mainly from the broad schizophrenic and affective spectrum, could suffer from mild neuroinflammation, which remained undetected because hard to diagnose with available diagnostic methods. Recently, in neurology an emerging new subgroup of autoimmune encephalitis (AE) cases suffering from various neurological syndromes was described in context with the discovery of an emerging list of Central Nervous System (CNS) autoantibodies. Similarly in psychiatry, consensus criteria of autoimmune psychosis (AP) were developed for patients presenting with CNS autoantibodies together with isolated psychiatric symptoms and paraclinical findings of (mild) neuroinflammation, which in fact match also the previously proposed ME criteria. Nevertheless, identifying mild neuroinflammation in the individual SMD case remains still a major clinical challenge and the possibility that further cases of ME remain still under diagnosed appears an plausible possibility. In this paper a critical review of recent developments and remaining challenges in the research and clinical diagnosis of mild neuroinflammation in SMDs and in general and in transdisciplinary perspective to psycho-neuro-immunology and neuropsychiatry is given. Present nosological classifications of neuroinflammatory disorders are reconsidered with regard to findings from experimental and clinical research. A refined grading list of clinical states including "classical" encephalitis, AE, AP/ME,and newly proposed terms like parainflammation, stress-induced parainflammation and neuroprogression, and their respective relation to neurodegeneration is presented, which may be useful for further research on the possible causative role of mild neuroinflammation in SMDs. Beyond, an etiology-focused subclassification of ME subtypes, like autoimmune ME or infectious ME, appears to be required for differential diagnosis and individualized treatment. The present status of the clinical diagnosis of mild neuroinflammatory mechanisms involved in SMDs is outlined with the example of actual diagnosis and therapy in AP. Ideas for future research to unravel the contribution of mild neuroinflammation in the causality of SMDs and the difficulties expected to come to novel immune modulatory, anti-infectious or anti-inflammatory therapeutic principles in the sense of precision medicine are discussed.
PubMed: 32973573
DOI: 10.3389/fpsyt.2020.00773 -
PloS One 2017Decompression sickness (DCS), which is caused by inert gas bubbles in tissues, is an injury of concern for scuba divers, compressed air workers, astronauts, and...
Decompression sickness (DCS), which is caused by inert gas bubbles in tissues, is an injury of concern for scuba divers, compressed air workers, astronauts, and aviators. Case reports for 3322 air and N2-O2 dives, resulting in 190 DCS events, were retrospectively analyzed and the outcomes were scored as (1) serious neurological, (2) cardiopulmonary, (3) mild neurological, (4) pain, (5) lymphatic or skin, and (6) constitutional or nonspecific manifestations. Following standard U.S. Navy medical definitions, the data were grouped into mild-Type I (manifestations 4-6)-and serious-Type II (manifestations 1-3). Additionally, we considered an alternative grouping of mild-Type A (manifestations 3-6)-and serious-Type B (manifestations 1 and 2). The current U.S. Navy guidance allows for a 2% probability of mild DCS and a 0.1% probability of serious DCS. We developed a hierarchical trinomial (3-state) probabilistic DCS model that simultaneously predicts the probability of mild and serious DCS given a dive exposure. Both the Type I/II and Type A/B discriminations of mild and serious DCS resulted in a highly significant (p << 0.01) improvement in trinomial model fit over the binomial (2-state) model. With the Type I/II definition, we found that the predicted probability of 'mild' DCS resulted in a longer allowable bottom time for the same 2% limit. However, for the 0.1% serious DCS limit, we found a vastly decreased allowable bottom dive time for all dive depths. If the Type A/B scoring was assigned to outcome severity, the no decompression limits (NDL) for air dives were still controlled by the acceptable serious DCS risk limit rather than the acceptable mild DCS risk limit. However, in this case, longer NDL limits were allowed than with the Type I/II scoring. The trinomial model mild and serious probabilities agree reasonably well with the current air NDL only with the Type A/B scoring and when 0.2% risk of serious DCS is allowed.
Topics: Decompression Sickness; Humans; Models, Theoretical; Probability
PubMed: 28296928
DOI: 10.1371/journal.pone.0172665 -
Dementia & Neuropsychologia 2013With the worldwide increase in longevity and rising prevalence of cognitive disorders in the aged population, efforts have been made to characterize mild cognitive... (Review)
Review
With the worldwide increase in longevity and rising prevalence of cognitive disorders in the aged population, efforts have been made to characterize mild cognitive impairment (MCI) and its prevalence and/or incidence in a number of countries, given MCI may be a pre-dementia phase of degenerative conditions. The aim of this review was to retrieve the available data on the prevalence and incidence of mild cognitive impairment (MCI) in Brazil and compare these with rates found by studies conducted in other countries. The Pubmed and Scielo databases were searched using the following search terms: mild cognitive impairment, prevalence, incidence, including studies in both English and Portuguese languages. Only one study on MCI prevalence has been published in Brazil, reporting a prevalence rate of 6.1% and incidence of 13.2/1000 persons-year among those aged 60 years or over. Prevalence rates for other countries are also reported. The prevalence and incidence of MCI found in Brazil is similar to rates observed in other countries.
PubMed: 29213859
DOI: 10.1590/S1980-57642013DN74000002 -
Frontiers in Neurology 2023gene pathogenic variations cause a spectrum of phenotypes, ranging from severe Duchenne muscular dystrophy, the Becker milder cases, the intermediate or very mild... (Review)
Review
deletions underlining mild dystrophinopathies: literature review highlights phenotype-related mutation clusters and provides insights about genetic mechanisms and prognosis.
gene pathogenic variations cause a spectrum of phenotypes, ranging from severe Duchenne muscular dystrophy, the Becker milder cases, the intermediate or very mild muscle phenotypes invariably characterized by high CK, and the ultrarare fully-asymptomatic cases. Besides these phenotypes, X-linked dilated cardiomyopathy is also caused by mutations. Males carrying deletions with absent or very mild phenotypes have been sparsely described. We performed a horizon scan on public datasets to enroll males with the above phenotypes and carrying deletions to delineate myopathic genotype-phenotype relationships. We inventoried 81 males, who were divided into the following clinical categorization: fully-asymptomatic males aged >43 years (A, = 22); isolated hyperCKemia (CK, = 35); and mild weakness (any age) with or without high CK (WCK, = 24). In all cases, deleted intervals were exons 2 to 55, and no downstream exons were ever involved, apart from an exon 78 deletion in a WCK patient. All deletions were in-frame apart from the known exception to the rule of exon 2 and exon 78. We correlated the mild phenotypes (A and CK) to deleted exons, intronic breakpoints, exon-exon junctions, 3' isoforms rule, and protein epitopes, and we found that some genetic profiles are exclusively/mainly occurring in A/CK phenotypes, suggesting they are compatible with a -normal muscular performance. We discussed diverse pathogenic mechanisms that may contribute to mild dystrophinopathic phenotypes, and we tried to address some "critical" genetic configurations or exon content needed to preserve a semi-functional gene.
PubMed: 38288333
DOI: 10.3389/fneur.2023.1288721 -
Frontiers in Cellular Neuroscience 2022Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI - "mild...
BACKGROUND
Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI - "mild neurocognitive disorder" (mild NCD) - this diagnosis is still based on clinical criteria.
METHODS
To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63-79 years old) were selected from the Leipzig-population-based study of adults (LIFE).
RESULTS
Serum S100B levels were increased in mild NCD in comparison to controls ( = 0.007. Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, = 0.01), independently of age.
CONCLUSION
Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD.
PubMed: 35910248
DOI: 10.3389/fncel.2022.788150