Symptoms Of Neurological Disorders Research Articles

BALB/c mice challenged with SARS-CoV-2 B.1.351 β variant cause pathophysiological and neurological changes within the lungs and brains.

Up to one-third of individuals suffering from acute SARS-CoV-2 infection with the onset of severe-to-mild diseases could develop several symptoms of neurological disorders, which could last long after resolving the infection, known as neuro-COVID. Effective therapeutic treatments for neuro-COVID remain unavailable, in part, due to the absence of animal models for studying its underlying mechanisms and developing medical countermeasures against it. Here, we explored the impact of SARS-CoV-2 infection on the well-being of respiratory and neurological functions of BALB/c mice by using a clinical isolate of β-variant, i.e. B.1.351. We found that this β-variant of SARS-CoV-2 primarily infected the lungs, causing tissue damage, profound inflammatory responses, altered respiratory functions and transient but significant hypoxia. Although live progeny viruses could not be isolated, viral RNAs were detected across many anatomical regions of the brains in most challenged mice and triggered activation of genes encoding for NF-kB, IL-6, IP-10 and RANTES and microglial cells. We noted that the significantly activated IL-6-encoded gene persisted at 4 weeks after infection. Together, these results suggest that this B.1.351/BALB/c model of SARS-CoV-2 infection warrants further studies to establish it as a desirable model for studies of neuropathogenesis and the development of effective therapeutics of neuro-COVID.

Fatigue Impacts Quality of Life in People with Spinocerebellar Ataxias.

Fatigue is a prevalent and debilitating symptom in neurological disorders, including spinocerebellar ataxias (SCAs). However, the risk factors of fatigue in the SCAs as well as its impact have not been well investigated. To study the prevalence of fatigue in SCAs, the factors contributing to fatigue, and the influence of fatigue on quality of life. Fatigue was assessed in 418 participants with SCA1, SCA2, SCA3, and SCA6 from the Clinical Research Consortium for the Study of Cerebellar Ataxia using the Fatigue Severity Scale. We conducted multi-variable linear regression models to examine the factors contributing to fatigue as well as the association between fatigue and quality of life. Fatigue was most prevalent in SCA3 (52.6%), followed by SCA1 (36.7%), SCA6 (35.7%), and SCA2 (35.6%). SCA cases with fatigue had more severe ataxia and worse depressive symptoms. In SCA3, those with fatigue had a longer disease duration and longer pathological CAG repeat numbers. In multi-variable models, depressive symptoms, but not ataxia severity, were associated with more severe fatigue. Fatigue, independent of ataxia and depression, contributed to worse quality of life in SCA3 and SCA6 at baseline, and fatigue continued affecting quality of life throughout the disease course in all types of SCA. Fatigue is a common symptom in SCAs and is closely related to depression. Fatigue significantly impacts patients' quality of life. Therefore, screening for fatigue should be considered a part of standard clinical care for SCAs.

Identification of Neural and Non-Neural Origins of Joint Hyper-Resistance Based on a Novel Neuromechanical Model.

Joint hyper-resistance is a common symptom in neurological disorders. It has both neural and non-neural origins, but it has been challenging to distinguish different origins based on clinical tests alone. Combining instrumented tests with parameter identification based on a neuromechanical model may allow us to dissociate the different origins of joint hyper-resistance in individual patients. However, this requires that the model captures the underlying mechanisms. Here, we propose a neuromechanical model that, in contrast to previously proposed models, accounts for muscle short-range stiffness (SRS) and its interaction with muscle tone and reflex activity. We collected knee angle trajectories during the pendulum test in 15 children with cerebral palsy (CP) and 5 typically developing children. We did the test in two conditions - hold and pre-movement - that have been shown to alter knee movement. We modeled the lower leg as an inverted pendulum actuated by two antagonistic Hill-type muscles extended with SRS. Reflex activity was modeled as delayed, linear feedback from muscle force. We estimated neural and non-neural parameters by optimizing the fit between simulated and measured knee angle trajectories during the hold condition. The model could fit a wide range of knee angle trajectories in the hold condition. The model with personalized parameters predicted the effect of pre-movement demonstrating that the model captured the underlying mechanism and subject-specific deficits. Our model may help with the identification of neural and non-neural origins of joint hyper-resistance and thereby opens perspectives for improved diagnosis and treatment selection in children with spastic CP, but such applications require further studies to establish the method's reliability.

13 Money versus Feedback: Comparing Reward Types and Frequency on Cognitive Fatigue

Objective:Cognitive fatigue (CF) is a common, yet poorly understood symptom in neurological disorders (e.g., multiple sclerosis, Parkinson’s disease, stroke). Studies show that reward plays a central role in CF. For instance, introducing or increasing reward often improves task performance. It is less clear, however, how reward affects subjective (self-reported) CF (SCF). This study examined the effect of reward type (monetary or performance feedback) and frequency (infrequent or frequent) on SF.Participants and Methods:In an online between-subjects study, 400 participants completed a computerized cognitive switching task and were randomly grouped into one of the five possible groups based on reward condition: [1] infrequent monetary reward, [2] frequent monetary reward, [3] infrequent performancefeedback reward, [4] frequent performance feedback reward, and [5] a no-reward group. SCF was assessed using the Visual Analog Scale of Fatigue (VAS-F) during the task. Mixed effects models were used to estimate the influence of reward type and frequency on task performance and SCF.Results:We found that the monetary groups were significantly faster (p<.001) compared to the feedback and no-reward groups, and that the frequent group was faster (p=.05) compared to the infrequent group. Reward type and frequency did not have a significant effect on VAS-F scores. However, when we looked at each reward group, we found that the monetary-infrequent reward group was associated with a decrease in VAS-F scores on average compared to the no-reward group (p=.04).Conclusions:The type and frequency of reward influence aspects of task performance (response time but not accuracy). Findings suggest that money had a greater effect on response time and may decrease SCF in cognitively healthy individuals when provided infrequently. Future studies should examine how these findings translate to clinical populations. Continued work is needed to understand how and which specific behavioral reward manipulations reduce fatigue, which could eventually lead to improved assessment and our ability to target fatigue across clinical populations.

Identification of motor progression in Parkinson’s disease using wearable sensors and machine learning

Wearable devices offer the potential to track motor symptoms in neurological disorders. Kinematic data used together with machine learning algorithms can accurately identify people living with movement disorders and the severity of their motor symptoms. In this study we aimed to establish whether a combination of wearable sensor data and machine learning algorithms with automatic feature selection can estimate the clinical rating scale and whether it is possible to monitor the motor symptom progression longitudinally, for people with Parkinson’s Disease. Seventy-four patients visited the lab seven times at 3-month intervals. Their walking (2-minutes) and postural sway (30-seconds,eyes-closed) were recorded using six Inertial Measurement Unit sensors. Simple linear regression and Random Forest algorithms were utilised together with different routines of automatic feature selection or factorisation, resulting in seven different machine learning algorithms to estimate the clinical rating scale (Movement Disorder Society- Unified Parkinson’s Disease Rating Scale part III; MDS-UPDRS-III). Twenty-nine features were found to significantly progress with time at group level. The Random Forest model revealed the most accurate estimation of the MDS-UPDRS-III among the seven models. The model estimations detected a statistically significant progression of the motor symptoms within 15 months when compared to the first visit, whereas the MDS-UPDRS-III did not capture any change. Wearable sensors and machine learning can track the motor symptom progression in people with PD better than the conventionally used clinical rating scales. The methods described in this study can be utilised complimentary to the clinical rating scales to improve the diagnostic and prognostic accuracy.

NeuralTree: A 256-Channel 0.227-μJ/Class Versatile Neural Activity Classification and Closed-Loop Neuromodulation SoC.

Closed-loop neural interfaces with on-chip machine learning can detect and suppress disease symptoms in neurological disorders or restore lost functions in paralyzed patients. While high-density neural recording can provide rich neural activity information for accurate disease-state detection, existing systems have low channel counts and poor scalability, which could limit their therapeutic efficacy. This work presents a highly scalable and versatile closed-loop neural interface SoC that can overcome these limitations. A 256-channel time-division multiplexed (TDM) front-end with a two-step fast-settling mixed-signal DC servo loop (DSL) is proposed to record high-spatial-resolution neural activity and perform channel-selective brain-state inference. A tree-structured neural network (NeuralTree) classification processor extracts a rich set of neural biomarkers in a patient- and disease-specific manner. Trained with an energy-aware learning algorithm, the NeuralTree classifier detects the symptoms of underlying disorders (e.g., epilepsy and movement disorders) at an optimal energy-accuracy trade-off. A 16-channel high-voltage (HV) compliant neurostimulator closes the therapeutic loop by delivering charge-balanced biphasic current pulses to the brain. The proposed SoC was fabricated in 65nm CMOS and achieved a 0.227μJ/class energy efficiency in a compact area of 0.014mm2/channel. The SoC was extensively verified on human electroencephalography (EEG) and intracranial EEG (iEEG) epilepsy datasets, obtaining 95.6%/94% sensitivity and 96.8%/96.9% specificity, respectively. In-vivo neural recordings using soft μECoG arrays and multi-domain biomarker extraction were further performed on a rat model of epilepsy. In addition, for the first time in literature, on-chip classification of rest-state tremor in Parkinson's disease (PD) from human local field potentials (LFPs) was demonstrated.

The link between cutaneous inflammation and cognitive impairment.

Cognitive impairment is a symptom of neurological disorders, including dementia and Alzheimer's disease; and mild cognitive impairment can be a precursor of both disorders. Aged humans and animal models with other systemic disorders, such as cardiovascular diseases and diabetes, display a higher incidence of cognitive decline. Epidemiological studies have shown that the incidence of cognitive impairment also is higher in subjects with certain inflammatory skin disorders, including psoriasis and chronic eczematous dermatitis. Chronologically aged individuals exhibit increased cutaneous inflammation and elevated circulating cytokine levels, linked to alterations in epidermal function, which itself can induce cutaneous inflammation. Conversely, strategies that improve epidermal function can lower cytokine levels in both the skin and circulation. Thus, it seems likely that epidermal dysfunction could contribute, at least in part, to the development of chronic low-grade inflammation, also termed 'inflammaging', in the elderly. The evidence of cognitive impairment in patients with inflammatory dermatoses suggests a link between cutaneous inflammation and cognitive impairment. Because of the pathogenic role of epidermal dysfunction in ageing-associated cutaneous inflammation, improvements in epidermal function could be an alternative approach for mitigation of the ageing-associated decline in cognitive function.

Non-invasive brain stimulation and psychiatric symptoms in neurological disorders

Psychiatric disorders are increasingly recognized as resulting from dysfunction in distributed neural circuitry. The ability of noninvasive brain stimulation to selectively target the circuitry underlying psychiatric disorders has made them valuable tools to study and treat a growing list of conditions including treatment resistant depression, obsessive compulsive disorder, and smoking dependence. FDA approved noninvasive devices for clinical treatment in psychiatry include transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and vagus nerve stimulation (VNS). There is also a range of other noninvasive brain stimulation tools at various stages of research that show promise, including transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST), and focused ultrasound (FUS). Since the initial approval of TMS in 2008, a growing number of devices, coils, and dosing strategies have become available that have the potential to reach a broader range of brain regions and accelerate therapeutic response. Research demonstrates that certain forms of TMS, when given simultaneously with cognitive training, may improve selected cognitive functions. Given the high degree of co-morbidity between neurological and psychiatric disorders, these development in noninvasive neuromodulation tools offer alternatives for neurological patients experiencing psychiatric symptoms. The availability to target neuromodulation via neuronavigation may be particularly useful in neurological patients with focal brain lesions. This presentation will review the state of the art of non-invasive neuromodulation tools in psychiatric care and will highlight the latest work with TMS for depression and cognitive function in patients with neurological disorders such as traumatic brain injury, stroke, and neurodegenerative disorders.

Self-Medication with Ganoderma lucidum ("Reishi") to Combat Parkinson's Disease Symptoms: A Single Case Study.

Parkinson's disease (PD) is a prevalent neurodegenerative disease for which only symptomatic treatments, mainly focused on motor symptoms. In contrast, conventional pharmacological treatments do not address cognitive impairment and emotional dysfunction. Together with potential treatment side effects, these can cause distress, lower the quality of life, and increase motor impairment in patients. Preclinical research suggests that the Traditional Chinese Medicine Ganoderma lucidum (“Reishi”) can alleviate symptoms in neurological disorders like PD. However, no clinical research to date has addressed this. An (unmedicated) patient, 50 years of age and diagnosed with PD for 5 years, approached the author as he decided to initiate self-treatment with Reishi, lasting 3 months. He wanted to evaluate the effects and decide to continue self-treatment or not. He agreed to be followed during this period, using questionnaires asking him about his (non-)motor symptoms. The most notable finding was the increase in Mindfulness, 3 months after self-treatment started. The motor symptoms stayed stable, there were no extreme changes in quality of life, and emotion regulation seemed to deteriorate over time while slightly improving at the 3-month assessment. While the findings do not allow firm conclusions seen the nature (N = 1) of this study, the small positive changes in some facets of affective behavior and the patient's experience, combined with the evidence from preclinical research, warrant clinical studies in this patient population.

Insomnia in neurological diseases

Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia – namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.

Gastrointestinal motility disorders in neurologic disease.

The extrinsic and autonomic nervous system intricately controls the major functions of the gastrointestinal tract through the enteric nervous system; these include motor, secretory, sensory, storage, and excretory functions. Disorders of the nervous system affecting gastrointestinal tract function manifest primarily as abnormalities in motor (rather than secretory) functions. Common gastrointestinal symptoms in neurologic disorders include sialorrhea, dysphagia, gastroparesis, intestinal pseudo-obstruction, constipation, diarrhea, and fecal incontinence. Diseases of the entire neural axis ranging from the cerebral hemispheres to the peripheral autonomic nerves can result in gastrointestinal motility disorders. The most common neurologic diseases affecting gastrointestinal function are stroke, parkinsonism, multiple sclerosis, and diabetic neuropathy. Diagnosis involves identification of the neurologic disease and its distribution, and documentation of segmental gut dysfunction, typically using noninvasive imaging, transit measurements, or intraluminal measurements of pressure activity and coordination of motility. Apart from treatment of the underlying neurologic disease, management focuses on restoration of normal hydration and nutrition and pharmacologic treatment of the gut neuromuscular disorder.

Neurogenic dysphagia in traditional Chinese medicine.

BackgroundNeurogenic dysphagia is the difficulty in swallowing caused by neurological diseases, which is a very common symptom in neurological disorders. In this paper, we try to summarize the opinions in the pathophysiology and therapy of dysphagia in ancient China (before AD 1840) through the records in the literatures from all the dynasties.MethodsWe searched the databases including Chinese Medical Classics, China National Knowledge Infrastructure, Wanfang Data, MEDLINE, and ISI Proceedings until July 2020, with the search terms “dysphagia” and “difficulty in swallowing” in English and their Chinese equivalents.Results and ConclusionsThe concept of neurogenic dysphagia was first described as Hou Bi in the Yellow Emperor's Internal Classic, which is the first Chinese medical classic and the origin of traditional Chinese medicine (TCM) theory. In the different eras, the pathogenesis of neurogenic dysphagia was explained mainly by three theories in TCM, that is, the wind‐phlegm blocking collaterals, the deficiency of liver and kidney‐essence, and the Qi‐stagnation with static blood. In addition to the TCM prescriptions, acupuncture is characteristic treatment and seems to be effective. However, the evidences of efficacy and safety from clinical trials are still required.

A Novel Graphic Medicine Curriculum for Resident Physicians: Boosting Empathy and Communication through Comics.

Curricular design that addresses residency physician competencies in communication skills and professionalism remains a challenge. Graphic Medicine (GM) uses comics, a medium combining text and images, to communicate healthcare concepts. Narrative Medicine, in undergraduate medical education, has limited reported usage in Graduate Medical Education (GME). Given the time constraints and intensity of GME, we hypothesized that comics as a form of narrative medicine would be an efficient medium to engage residents.The authors created a novel curriculum to promote effective communication and professionalism, focusing on empathy, compassion and cultural competency. A four-week curriculum was delivered in a neurology residency program. Excerpts from non-fiction graphic memoirs about neurological conditions were read, discussed, and paired with prompt-driven drawing exercises. Qualitative surveys were used to assess acceptability of comics, usefulness of comics to convey patient illness experience, and perception of patient needs for physician-patient communication.Ninety-seven percent of residents reported the sessions were a good use of their time. Residents identified new symptoms of neurologic disorders, articulated patient communication needs, and expressed increased empathy after participation. Residents participated in drawing exercises, but these were not formally analyzed. Graphic medicine is a well received format that may build communication skills and increase empathy.

Using Virtual Reality to Improve Apathy in Residential Aged Care: Mixed Methods Study

BackgroundApathy is a common symptom in neurological disorders, including dementia, and is associated with a faster rate of cognitive decline, reduced quality of life, and high caregiver burden. There is a lack of effective pharmacological treatments for apathy, and nonpharmacological interventions are a preferred first-line approach to treatment. Virtual reality (VR) using head-mounted displays (HMDs) is being successfully used in exposure- and distraction-based therapies; however, there is limited research on using HMDs for symptoms of neurological disorders.ObjectiveThis feasibility study aimed to assess whether VR using HMDs could be used to deliver tailored reminiscence therapy and examine the willingness to participate, response rates to measures, time taken to create tailored content, and technical problems. In addition, this study aimed to explore the immediate effects between verbal fluency and apathy after exposure to VR.MethodsA mixed methods study was conducted in a sample of older adults residing in aged care, and 17 participants were recruited. Apathy was measured using the Apathy Evaluation Scale (AES), and verbal fluency was used as a proxy measure of improvements in apathy and debriefing interviews to assess feedback from participants. Side effects that can occur from using HMDs were also measured.ResultsWe recruited participants from a high socioeconomic status setting with a high education level, and the participation rate was 85% (17/20); most responses to measures were positive. Access to a wide range of freely available content and the absence of technical difficulties made the delivery of a VR reminiscence intervention highly feasible. Participants had improved semantic scores (t14=−3.27; P=.006) but not phonemic fluency scores (t14=0.55; P=.59) immediately after the intervention. Those with higher levels of apathy demonstrated the greatest cognitive improvements after a VR reminiscence experience, which was indicated by a strong positive relationship between the AES and semantic verbal fluency change scores postminus pre-VR (r=0.719; 95% CI 0.327 to 0.900; P=.003). All participants enjoyed the experience despite 35% (6/17) of participants experiencing temporary side effects.ConclusionsThis study provides initial evidence that it is feasible to use VR with HMDs for therapy to treat symptoms of apathy in older adults in residential aged care. However, there is a need to closely monitor the side effects of HMD use in older adults. Further research is needed using an active control group to compare the use of VR with traditional forms of reminiscence therapy.

Case report: a child with cystic fibrosis and phenylketonuria

Background. In the international clinical practice there have been occasional reports of phenylketonuria (PKU) and cystic fibrosis (CF) found simultaneously in the same patient. Both PKU and CF are the inherited disorders characterized by autosomal recessive type of inheritance. Currently the combination of two or more inherited disorders in one patient is considered to be a clinical rarity.Case description. This is a clinical case of two genetic disorders, CF and PKU, combined in a 5-year old patient who had been followed up since birth. Owing to implementation of neonatal screening for inherited and congenital diseases into clinical practice, during the first month of life the infant was diagnosed with CF (diagnostically significant elevation of immunoreactive trypsin [IRT] at the initial [163.2 ng/mL] and repeat testing on day 21 of life [138.7 ng/mL]) and PKU (phenylalanine [PA] level 15.9 mg/dL). Both disorders have been confirmed by genetic tests, i.e., homozygous DelF508 mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and P281L mutation in the phenylalanine hydroxylase (PAH) gene was also present in homozygous state. Child’s parents strictly adhered to dietary and treatment recommendations. By the age of 5 years the child developed symptoms of neurological disorder and disorder of the respiratory system, cognitive impairment and delay in speech development, subclinical epileptiform activity with high risk of epilepsy, and chronic inflammation of the respiratory tract.Conclusion. This case report demonstrates the important role of neonatal screening in early diagnosis and timely start of therapy, and underscores the importance of continuous medication in such genetic disorders as CF and PKU. On the whole, such approach brings about a relative preservation of functioning of the most affected organs and systems. By the age of 5 years the child does not form bronchiectases, shows no signs of chronic hypoxia, nutritional deficiency or pronounced neurologic deficit, and is at low risk for the development of autism spectrum disorder. At the same time, the larger scale and longer-term observations are required in order to make the unequivocal conclusions about the prognosis of these diseases under conditions of modern-day medical follow-up.

Case report: a child with cystic fibrosis and phenylketonuria

Background. In the international clinical practice there have been occasional reports of phenylketonuria (PKU) and cystic fibrosis (CF) found simultaneously in the same patient. Both PKU and CF are the inherited disorders characterized by autosomal recessive type of inheritance. Currently the combination of two or more inherited disorders in one patient is considered to be a clinical rarity.Case description. This is a clinical case of two genetic disorders, CF and PKU, combined in a 5-year old patient who had been followed up since birth. Owing to implementation of neonatal screening for inherited and congenital diseases into clinical practice, during the first month of life the infant was diagnosed with CF (diagnostically significant elevation of immunoreactive trypsin [IRT] at the initial [163.2 ng/mL] and repeat testing on day 21 of life [138.7 ng/mL]) and PKU (phenylalanine [PA] level 15.9 mg/dL). Both disorders have been confirmed by genetic tests, i.e., homozygous DelF508 mutation was found in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and P281L mutation in the phenylalanine hydroxylase (PAH) gene was also present in homozygous state. Child’s parents strictly adhered to dietary and treatment recommendations. By the age of 5 years the child developed symptoms of neurological disorder and disorder of the respiratory system, cognitive impairment and delay in speech development, subclinical epileptiform activity with high risk of epilepsy, and chronic inflammation of the respiratory tract.Conclusion. This case report demonstrates the important role of neonatal screening in early diagnosis and timely start of therapy, and underscores the importance of continuous medication in such genetic disorders as CF and PKU. On the whole, such approach brings about a relative preservation of functioning of the most affected organs and systems. By the age of 5 years the child does not form bronchiectases, shows no signs of chronic hypoxia, nutritional deficiency or pronounced neurologic deficit, and is at low risk for the development of autism spectrum disorder. At the same time, the larger scale and longer-term observations are required in order to make the unequivocal conclusions about the prognosis of these diseases under conditions of modern-day medical follow-up.

The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders.

Mucus is integral to gut health and its properties may be affected in neurological disease. Mucus comprises a hydrated network of polymers including glycosylated mucin proteins. We propose that factors that influence the nervous system may also affect the volume, viscosity, porosity of mucus composition and subsequently, gastrointestinal (GI) microbial populations. The gut has its own intrinsic neuronal network, the enteric nervous system, which extends the length of the GI tract and innervates the mucosal epithelium. The ENS regulates gut function including mucus secretion and renewal. Both dysbiosis and gut dysfunction are commonly reported in several neurological disorders such as Parkinson's and Alzheimer's disease as well in patients with neurodevelopmental disorders including autism. Since some microbes use mucus as a prominent energy source, changes in mucus properties could alter, and even exacerbate, dysbiosis-related gut symptoms in neurological disorders. This review summarizes existing knowledge of the structure and function of the mucus of the GI tract and highlights areas to be addressed in future research to better understand how intestinal homeostasis is impacted in neurological disorders.

Employing an ICT-FRET Integration Platform for the Real-Time Tracking of SO2 Metabolism in Cancer Cells and Tumor Models

Glutathione (GSH) mediates a wide variety of biological events and human diseases. Although it has been the subject of intense study in recent years, a further understanding of its molecular mechanisms and metabolism routes in living cells has remained limited due to a lack of appropriate analytical tools. Sulfur dioxide (SO2), an important metabolite of GSH, is usually associated with the symptoms of neurological disorders, cardiovascular diseases, and lung cancer. Herein, a novel multisignal fluorescent probe was rationally designed and exploited for the simultaneous detection of GSH and its metabolite SO2 via an ICT-FRET synergetic mechanism. The probe shows completely reversed fluorescence responses toward GSH (enhanced red emission) and SO2 (annihilated red fluorescence) with high selectivity and sensitivity. In particular, the probe displayed completely different fluorescent signals (blue-shift) with SO2 in the presence of GSH, thereby allowing the imaging of the metabolism process of GSH to SO2 in two independent channels without spectral cross interference. Given these advantages, this probe has been successfully applied to the real-time monitoring of the SO2 metabolic process in living cells and mice models, and it has thus been found that GSH can metabolize SO2 by enzymatic reaction with TST (thiosulfate sulphurtransferase); additionally, SO2 was transformed into sulfate under SUOX (sulfite oxidase). We anticipate that this research will provide a convenient and efficient tool for understanding the interrelated physiological functions of GSH and SO2 in more biosystems.

Evaluation of changes in lymphocyte to monocyte ratio in stroke subgroups

Abstract Backround: Stroke is one of the most important disease causing serious morbidity and mortality worldwide. There are some studies showing the change in hematological inflammatory markers in stroke patients. Lymphocyte to monocyte ratio (LMR) is considered to be a new hematological inflammatory marker that has been recently investigated in many malignancies with its particularly low level. In this study, we aimed to evaluate the levels of LMR in patients presented to our emergency department with neurological findings, diagnosed as ischemic stroke and also we aimed to evaluate the levels of LMR in subgroups according to the Oxfordshire Community Stroke Project (OCSP) classification which is a clinical classification. Material and Methods: The patients admitted to the emergency department of a university hospital with symptoms of neurological disorders and diagnosed with ischemic stroke between January 2017 and January 2019 were retrospectively analyzed. Stroke patients were divided into subgroups according to OCSP classification and clinical and imaging results were correlated. Hematologic inflammatory markers were examined in all groups and changes in LMR were detected. Results: 109 (63 female, 46 male) ischemic stroke patients and 110 (45 female, 65 male) control patients were included in the study. The low LMR values were found to be statistically significant in stroke cases compared to the control group (p <0.05). The low LMR values were found to be statistically significant in all four subgroups compared to the control group (p <0.05). TACI and POCI groups showed the lowest mean in LMR values. Higher NLR and GGT values were found to be statistically significant in all four groups compared to the control group (p <0.05). Conclusion: In our study, the LMR value, which was limited investigated in stroke subgroups, was found to be low in all stroke and subgroups. Especially in clinical situations with large infarct sizes such as TACI and POCI groups, the lowest means were reached. It is thought that LMR can be used as a predictor of mortality, morbidity, and prognosis in both stroke and its subgroups.

Neurological Complications After Renal Transplantation: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the prevalence of neurological complication after renal transplantation. The searches were conducted by two independent researchers in the international (PubMed, Web of Science, Scopus, and Google Scholar) and national databases (Magiran and SID) to find the relevant studies published in English and Persian languages since the creation of the databases until January 2019 (without time limitations). The keywords used in the search strategy were: neurologic complication, central nervous system, peripheral nervous system, tremor, CVA, encephalopathy, neurological complications, renal transplantation, renal failure, kidney transplantation, immunosuppression, neurotoxicity, opportunistic infections, CNS, cerebrovascular disease, chronic kidney disease, cognitive impairment, and end-stage renal disease, which were combined using the AND, OR, and NOT operators. Finally, a meta-analysis was conducted in STATA14 statistical software. Based on the random effect model, the total prevalence of neurologic complications in 4674 patients who had undergone the renal transplantation surgery was 7.9% (95% confidence interval [CI]:7.2%,8.7%, I2 = 90.1%). The prevalence of infectious, non-infectious and treatment associated neurologic complications was 9.5% (95% CI -8.9, 10.2), 91.8% (95% CI -91.3, 92.4) and 97% (95% CI-95.7%,98.4%) of all neurologic complications in renal transplant patients, respectively. And according to the present subgroup analysis, peripheral neuropathy with a prevalence about 30% (29%) (95% CI -27.6%, 30.4%, I2 = 99.4%) was the most common neurological disorder in renal transplant patients followed by tremor with a prevalence of 19.5% (CI -17.6%, 21.3%, I2 = 97.1%), cerebrovascular events with a prevalence of 15.1% (95% CI -13.9%, 16.4%, I2 = 96.5%), encephalopathy with the prevalence of 13% (95% CI -12%, 14%, I2 = 99.3%), headache with a prevalence of 8.3% (95% CI -6.8%, 9.8%, I2 = 97.3%) and seizure with a prevalence of 7.4% (CI - 6.5%, 8.3%, I2 = 94.6%). The results of the present systematic review and meta-analysis, suggests that post-kidney transplantation neurological disorders, with a prevalence rate about 8%, are relatively common; most of them are caused by immunosuppressive drugs and can be treated by decreasing the dose or switching the immunosuppressive drugs. Neurological disorders are associated with increased mortality; thus, differential diagnosis should be conducted for each individual patient with neurological symptoms after transplantation. It is important for all health care providers to become familiar with the symptoms of neurological disorders that may occur after organ transplants. Recognizing and monitoring these symptoms can reduce the risk of death in kidney transplant recipients. Further research is needed to help the transplant community to identify these issues and problems better in order to achieve the ultimate goal of helping renal patients and sending them back into their normal lives.