Aquaporin 4 beyond a water channel; participation in motor, sensory, cognitive and psychological performances, a comprehensive review.

Aquaporin 4 (AQP4) is a protein highly expressed in the central nervous system (CNS) and peripheral nervous system (PNS) as well as various other organs, whose different sites of action indicate its importance in various functions. AQP4 has a variety of essential roles beyond water homeostasis. In this article, we have for the first time summarized different roles of AQP4 in motor and sensory functions, besides cognitive and psychological performances, and most importantly, possible physiological mechanisms by which AQP4 can exert its effects. Furthermore, we demonstrated that AQP4 participates in pathology of different neurological disorders, various effects depending on the disease type. Since neurological diseases involve a spectrum of dysfunctions and due to the difficulty of obtaining a treatment that can simultaneously affect these deficits, it is therefore suggested that future studies consider the role of this protein in different functional impairments related to neurological disorders simultaneously or separately by targeting AQP4 expression and/or polarity modulation.

Focusing on the locus of the breakdown for treatment of anomia: a pilot study.

The primary goal of this study was to evaluate the treatment effects of semantic feature analysis (SFA) and phonological components analysis (PCA) on word retrieval processing in persons with aphasia (PWAs). After identifying the locus of the breakdown in lexical retrieval processing, 15 monolingual native Persian speakers with aphasia were divided into two groups. After three naming trials, participants with dominant semantic deficits received SFA, and participants with primary phonological deficits were provided with PCA three times a week for eight weeks. Both approaches improved participants' naming and performance on language tests, including spontaneous speech, repetition, comprehension, and semantic processing. However, the correct naming of treated and untreated items was higher in mild-to-moderate participants, with mostly circumlocution and semantic paraphasias in the SFA group. The same holds for mild-to-moderate participants with mostly phonemic paraphasia who received PCA therapy. Moreover, the results showed that participants' baseline naming performance and semantic abilities could be associated with the treatment outcomes. Although limited by a lack of a control group, this study provided evidence supporting the possible benefits of focusing on the locus of the breakdown for treating anomia through SFA and PCA approaches, specifically in participants with mild to moderate aphasia. However, for those with severe aphasia, the treatment choice may not be as straightforward because several variables are likely to contribute to this population's word-finding difficulties. Replication with larger, well-stratified samples, use of a within-subjects alternating treatment design and consideration of treatments' long-term effects are required to better ascertain the effects of focusing on the locus of breakdown for treatment of anomia.

Low-dose sumatriptan improves the outcome of acute mesenteric ischemia in rats via downregulating kynurenine.

BACKGROUND: Mesenteric ischemia has remained without effective pharmacological management for many years. Sumatriptan, an abortive medication for migraine and cluster headaches, has potent anti-inflammatory properties and ameliorated organ ischemia in previous animal studies. Similarly, inhibition of the kynurenine pathway ameliorated renal and myocardial ischemia/reperfusion (I/R) in many preclinical studies. Herein, we assessed the effect of sumatriptan on experimental mesenteric I/R and investigated whether kynurenine pathway inhibition is a mechanism underlying its action. METHODS: Ischemia was induced by ligating the origin of the superior mesenteric artery (SMA) and its anastomosis with the inferior mesenteric artery (IMA) with bulldog clamps for 30 min. Ischemia was followed by 1 h of reperfusion. Sumatriptan (0.1, 0.3, and 1 mg/kg ip) was injected 5 min before the reperfusion phase, 1-methyltryptophan (1-MT) (100 mg/kg iv) was used to inhibit kynurenine production. At the end of the reperfusion phase, samples were collected from the jejunum of rats for H&E staining and molecular assessments. RESULTS: Sumatriptan improved the integrity of intestinal mucosa after I/R, and 0.1 mg/kg was the most effective dose of sumatriptan in this study. Sumatriptan decreased the increased levels of TNF-α, kynurenine, and p-ERK but did not change the decreased levels of NO. Furthermore, sumatriptan significantly increased the decreased ratio of Bcl2/Bax. Similarly, 1-MT significantly decreased TNF-α and kynurenine and protected against mucosal damage. CONCLUSIONS: This study demonstrated that sumatriptan has protective effects against mesenteric ischemia and the kynurenine inhibition is potentially involved in this process. Therefore, it can be assumed that sumatriptan has the potential to be repurposed as a treatment for acute mesenteric ischemia.

Minimal clinically important difference of the King's Parkinson's disease Pain Scale.

OBJECTIVE: Pain is a common and debilitating symptom of Parkinson's disease (PD) and has no specific treatment. King's Parkinson's disease Pain Scale (KPPS) is the only specific scale for pain measurement in PD with established psychometric properties. The minimal clinically important difference (MCID) of KPPS, an important parameter for the design and interpretation of therapeutic interventions, has not yet been measured. The aim of our study was to assess the MCID of KPPS. METHODS: Two hundred and seven PD patients were evaluated by KPPS before and after receiving the intervention. The Clinical Global Impression of Improvement Scale was used as an anchor, and a Receiver Operating Characteristic (ROC) curve was used to determine the optimal MCID cut-off point for KPPS. The distribution-based approach applied one-third standard deviation (SD), 0.5 SD, and one standard error of measurement (SEM) of the total score of KPPS to determine the MCID. RESULTS: The MCID achieved from the ROC curve was 3 points (sensitivity: 74.4%; specificity: 81.9%). For the distribution-based method, the MCIDs corresponding to 0.3 SD, 0.5 SD, and one SEM were 5.65, 9.41, and 2.54 points, respectively. CONCLUSION: KPPS is a valid scale for measuring pain in PD with demonstrable MCID. IMPLICATIONS FOR REHABILITATIONThe King's Parkinson's disease Pain Scale (KPPS) is a valid scale for measuring pain in patients with Parkinson's disease (PD) with demonstrable minimal clinically important difference (MCID).The MCID obtained in the current study will assist clinicians and researchers when interpreting KPPS change score to determine clinically meaningful changes of pain in both PD progression and response to interventions.

Mechanisms of brain activation following naming therapy in aphasia: A systematic review on task-based fMRI studies.

The pattern of brain neuroplasticity after naming therapies in patients with aphasia can be evaluated using task-based fMRI. This article aims to review studies investigating brain reorganization after semantic and phonological-based anomia therapy that used picture-naming fMRI tasks. We searched for those articles that compared the activation of brain areas before and after aphasia therapies in the PubMed and the EMBASE databases from 1993 up to April 2020. All studies (single-cases or group designs) on anomia treatment in individuals with acquired aphasia were reviewed. Data were synthesized descriptively through tables to allow the facilitated comparison of the studies. A total of 14 studies were selected and reviewed. The results of the reviewed studies demonstrated that the naming improvement is associated with changes in the activation of cortical and subcortical brain areas. This review highlights the need for a more systematic investigation of the association between decreased and increased activation of brain areas related to anomia therapy. Also, more detailed information about factors influencing brain reorganization is required to elucidate the neural mechanisms of anomia therapy. Overall, regarding the theoretical and clinical aspects, the number of studies that used intensive protocol is growing, and based on the positive potential of these treatments, they could be suitable for the rehabilitation of people with aphasia.

The N-methyl-D-aspartate receptor antagonist ketamin exerts analgesic effects via modulation of the nitric oxide pathway.

Ketamine, an NMDA receptor antagonist, has been approved to have analgesic effects. It is known that nitric oxide pathway is involved in antinociception but with dual effects. In this study, we investigated the role of nitric oxide in ketamine-induced analgesia. Ketamine was administered to mice acute and chronically with/without nitric oxide synthase (NOS) inhibitors. Experimental models of nociception pain, including hot plate, tail flick, and formalin tests, were performed. Western blot was used to measure levels of nitric oxide synthase enzymes in the brain. Ketamine doses of 0.03 and 0.3 mg/kg had significant analgesic effects (p < 0.01). High-dose chronic ketamine could induce analgesia in later phases of the treatment in tail flick test (p < 0.01). Pretreatment with various NOS inhibitors decreased the analgesic effect. In western blot analysis, the expression of NOS proteins was decreased. Low-dose ketamine is effective in analgesia induction. The expression of nNOS and iNOS proteins is dependent on the inhibition of the NMDA/NO pathway.

Psychometric properties of dexterity questionnaire-24 in Iranian chronic stroke survivors.

INTRODUCTION: Dexterity is one of the most critical upper extremity functions that may be impaired in chronic stroke survivors. This study aimed to investigate the psychometric properties of DextQ-24 in Iranian chronic stroke survivors. METHOD: A total of 123 people with chronic stroke were included in the study. Internal consistency and test-retest reliability were assessed through Cronbach's alpha and Interclass Correlation (ICC), respectively. Dimensionality was performed by Exploratory Factor Analysis. In addition, to assess the convergent validity of DextQ-24, Box and Block Test, Motor Activity Log Questionnaire, ABILHAND Questionnaire, and Purdue Pegboard Test were used. Discriminant validity of DextQ-24 was measured between different stages of recovery (Brunnstrom stage). Acceptability was calculated by ceiling and floor effect. RESULTS: Cronbach's alpha and ICC were 0.92 and 0.91, respectively. The 24 items of this questionnaire were classified into six components. Further, a moderate to strong correlation between the total score of DextQ-24 with other tools | r = 0.41-0.84 | was obtained. The results of discriminant validity approved the ability of the total score of DextQ-24 to separate different stages of recovery. The results also reported that this questionnaire did not have a significant ceiling and floor effect. CONCLUSION: The results of our study showed that the Persian DextQ-24 has high reliability and a good convergent and discriminant validity in people with chronic stroke for dexterity measurement as a PROM questionnaire.

Psychometric features of brief pain inventory for Parkinson's disease during medication states.

PURPOSE: Patients with idiopathic Parkinson's disease (PD) suffer from different non-motor symptoms, including pain. The present study aimed to measure the psychometric properties of the Brief Pain Inventory (BPI) in patients with PD during ON- and OFF-states. METHODS: We recruited 460 patients with PD and 100 non-PD controls. The pain was assessed by the BPI, King's Parkinson's disease Pain Scale (KPPS), Neuropathic Pain Symptom Inventory (NPSI), Visual Analogue Scale-Pain (VAS-pain), and short-form McGill Pain Questionnaire-2 (SF-MPQ-2) in both medication states. Internal consistency and test-retest reliability was examined using Cronbach's alpha coefficient and intra-class correlation coefficient (ICC). Dimensionality and convergent validity of BPI were also investigated. Diagnostic accuracy and discriminative validity were determined by Receiver Operating Characteristics (ROC) curve analysis and Area Under the Curve (AUC). RESULTS: Cronbach's alpha was satisfactory (α = 0.91-0.97) in both states. The ICC values were 0.85-0.96 in ON- and OFF-state. Factor analysis revealed two factors. A high correlation was obtained between BPI subscales and other scales. AUC >0.91, sensitivity, and specificity> 0.77 were observed for discriminating different pain levels. Furthermore, appropriate diagnostic accuracy was found (AUC, sensitivity, and specificity >0.67) between non-PD control and PD patients. CONCLUSION: The BPI has acceptable psychometric features as well as diagnostic accuracy for patients with PD.Implications for rehabilitationPain as a non-motor symptom in PD can affect daily and social activities.The BPI is used to assess pain severity and interference in activities.For better treatment, pain should be assessed in off-state like to on-state.BPI has satisfactory reliability and validity in different medication states in PD.

Validity and Reliability of the Persian Version of Parkinson's Disease Sleep Scale-2.

OBJECTIVE: Sleep problems are nonmotor symptoms in Parkinson's disease that should be carefully evaluated for better management and treatment. Parkinson's Disease Sleep Scale (PDSS-2) is one of the most reliable tools for measuring sleep difficulties in people with Parkinson's disease. This study investigated the psychometric properties of the Persian version of PDSS-2. METHODS: Four hundred and fifty-six people with Parkinson's disease with a mean age ±standard deviation of 60.7 ± 11.3 years were engaged in this study. Acceptability was assessed by floor and ceiling effects. Dimensionality was measured by exploratory factor analysis. The convergent validity of PDSS-2 with the Hospital Anxiety and Depression Scale (HADS) was assessed. Internal consistency and test-retest reliability were assessed with Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. RESULTS: No noticeable ceiling and floor effect was detected. The dimensionality analysis showed three factors. A high correlation was obtained between PDSS-2 and HADS (anxiety subscale). Excellent internal consistency with α = 0.94, and good test-retest reliability with ICC = 0.89 were obtained. CONCLUSION: This study showed that the Persian version of Parkinson's Disease Sleep Scale has acceptable validity and reliability for measuring sleep disturbances in people with Parkinson's disease.

Insights Into Parkin-Mediated Mitophagy in Alzheimer's Disease: A Systematic Review.

Background: Parkin-mediated mitophagy is the dominant mitophagy pathway of neural cells. Its restoration will result in prevention of cognitive decline, including Alzheimer's disease (AD). The role of this mitophagy pathway in neurodegenerative diseases has drawn attention in recent years. The two main pathological proteins in AD, amyloid ß (Aß) and human Tau (hTau), interfere with mitochondrial dynamics through several pathways. However, taking into consideration the specific interactions between Aß/hTau and Parkin, special focus is required on this mitophagy pathway and AD. In this review, these interactions are fully discussed, and an overview of the neuroprotective drugs that enhance Parkin-mediated mitophagy is presented. Methods: This systematic review was performed according to PRISMA guidelines, and a comprehensive literature search was done in the electronic databases up to September 2020, using search terms in the titles and abstracts to identify relevant studies. One hundred eighty-six articles were found, and 113 articles were screened by title and abstract. Finally, 25 articles were included in this systematic review according to our inclusion and exclusion criteria. Results: Accumulation of Aß and hTau affects mitophagy, including Parkin-mediated. Tau seems to prevent Parkin translocation directly. A Parkin level in the cell appears to be of importance in determining the damage caused by Aß and hTau and in the future therapeutic approaches. Parkin controls the PINK1 level via the presenillins, suggesting that mutations in presenillins affect Parkin mitophagy. Significance: Parkin mitophagy is a process affected by several AD pathological events multidimensionally.

Extreme capsule is a bottleneck for ventral pathway.

As neuroscience literature suggests, extreme capsule is considered a whiter matter tract. Nevertheless, it is not clear whether extreme capsule itself is an association fiber pathway or only a bottleneck for other association fibers to pass. Via our review, investigating anatomical position, connectivity and cognitive role of the bundles in extreme capsule, and by analyzing data from the dissection, it can be argued that extreme capsule is probably a bottleneck for the passage of uncinated fasciculus (UF) and inferior fronto-occipital fasciculus (IFOF), and these fasciculi are responsible for the respective roles in language processing.

King's Parkinson's disease pain scale cut-off points for detection of pain severity levels: A reliability and validity study.

BACKGROUND: Pain is one of the most common non-motor symptoms in Parkinson's disease (PD). Using an appropriate and specific measuring tool would be helpful in managing the pain. King's Parkinson's disease Pain Scale (KPPS) is an instrument designed to specifically measure pain in people with PD. PURPOSE: This study aimed to examine the psychometric properties of the Persian version of KPPS (KPPS-P) and its cut-off points for pain severity levels. METHODS: A total of 480 people with PD (with a mean (SD) age of 60.89 (10.98)) were recruited. The acceptability of KPPS-P was calculated. The structural validity and discriminant validity for different levels of pain was explored via the factor analysis, and Receiver Operating Characteristics (ROC) curves, respectively. Internal consistency, test-retest, and inter-rater reliability were estimated by Cronbach's alpha and Interclass Correlation coefficient (ICC). Convergent validity was established between KPPS-P and other scales including Visual Analog Scale-Pain, Douleur Neuropathic 4, Brief Pain Inventory, Short-form McGill Pain Questionnaire-2, and Parkinson's Disease-8. RESULTS: A significant floor effect was observed. The exploratory factor analysis revealed 4 factors. Cronbach's alpha and ICC values were higher than 0.80. The correlation range between KPPS-P and other scales was 0.35-0.76. Cut-off points of 0, 17, and 68 were obtained to discriminate pain severity levels between no pain, mild, moderate, and severe pain, respectively, with sensitivity and specificity above 0.80. CONCLUSION: Our results indicate that the Persian version of KPPS not only has acceptable psychometric properties to assess pain in PD but also has the ability to distinguish between different levels of pain severity.

Psychometric features of Neuropathic Pain Symptom Inventory in Iranian people with Parkinson's disease.

OBJECTIVE: Neuropathic pain is a type of pain reported in people with Parkinson's disease. There are various scales to evaluate the characteristics of this kind of pain. The purpose of this study was to investigate the psychometric properties of the Neuropathic Pain Symptom Inventory (NPSI), a specific scale that measures neuropathic pain in Iranian people with Parkinson's disease. METHOD: Four hundred forty-seven individuals with Parkinson's disease were recruited in the study. Acceptability, internal consistency (Cronbach's alpha), and test-retest reliability (intraclass correlation coefficient, ICC) of NPSI were calculated. Dimensionality was examined through exploratory factor analysis. For convergent validity, correlations of NPSI with Douleur Neuropathic 4, Brief Pain Inventory, King's Pain Parkinson disease Scale, and Visual Analog Scale-Pain were used. Discriminative validity and sensitivity to change between On- and Off- medication states were analyzed. RESULTS: A marked floor effect was observed for this scale (64.2%). Cronbach's alpha and ICC were 0.90 and 0.87, respectively. Items of NPSI were placed in 4 factors. A moderate to the strong association (rs = 0.55 to 0.85) between NPSI and other scales was obtained. The results of discriminative validity and sensitivity to change indicate the ability of NPSI to show differences between medication states. CONCLUSION: The results of this study suggest that NPSI has acceptable reliability, validity, and sensitivity to change, indicating that this scale is suitable for measuring neuropathic pain in Iranian people with Parkinson's disease.