Thalamic Alterations in Motor Neuron Diseases: A Systematic Review of MRI Findings.

BACKGROUND: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes. METHODS: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale. RESULTS: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs. CONCLUSIONS: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.

Quantitative Assessment of Resting-State Functional Connectivity MRI to Differentiate Amnestic Mild Cognitive Impairment, Late-Onset Alzheimer's Disease From Normal Subjects.

BACKGROUND: Alzheimer disease (AD) is a neurological disorder with brain network dysfunction. Investigation of the brain network functional connectivity (FC) alterations using resting-state functional MRI (rs-fMRI) can provide valuable information about the brain network pattern in early AD diagnosis. PURPOSE: To quantitatively assess FC patterns of resting-state brain networks and graph theory metrics (GTMs) to identify potential features for differentiation of amnestic mild cognitive impairment (aMCI) and late-onset AD from normal. STUDY TYPE: Prospective. SUBJECTS: A total of 14 normal, 16 aMCI, and 13 late-onset AD. FIELD STRENGTH/SEQUENCE: A 3.0 T; rs-fMRI: single-shot 2D-EPI and T1-weighted structure: MPRAGE. ASSESSMENT: By applying bivariate correlation coefficient and Fisher transformation on the time series of predefined ROIs' pairs, correlation coefficient matrixes and ROI-to-ROI connectivity (RRC) were extracted. By thresholding the RRC matrix (with a threshold of 0.15), a graph adjacency matrix was created to compute GTMs. STATISTICAL TESTS: Region of interest (ROI)-based analysis: parametric multivariable statistical analysis (PMSA) with a false discovery rate using (FDR)-corrected P < 0.05 cluster-level threshold together with posthoc uncorrected P < 0.05 connection-level threshold. Graph-theory analysis (GTA): P-FDR-corrected < 0.05. One-way ANOVA and Chi-square tests were used to compare clinical characteristics. RESULTS: PMSA differentiated AD from normal, with a significant decrease in FC of default mode, salience, dorsal attention, frontoparietal, language, visual, and cerebellar networks. Furthermore, significant increase in overall FC of visual and language networks was observed in aMCI compared to normal. GTA revealed a significant decrease in global-efficiency (28.05 < 45), local-efficiency (22.98 < 24.05), and betweenness-centrality (14.60 < 17.39) for AD against normal. Moreover, a significant increase in local-efficiency (33.46 > 24.05) and clustering-coefficient (25 > 20.18) were found in aMCI compared to normal. DATA CONCLUSION: This study demonstrated resting-state FC potential as an indicator to differentiate AD, aMCI, and normal. GTA revealed brain integration and breakdown by providing concise and comprehensible statistics. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Development of a serious game-based cognitive rehabilitation system for patients with brain injury.

BACKGROUND: Traumatic brain injury (TBI) resulting from a forceful impact to the head can cause severe functional disabilities, with cognitive impairment being a major hindrance to patients' return to daily life. Encouraging patients to engage in rehabilitation programs consistently poses a significant challenge for therapists. To address this issue, gamification has gained momentum as an effective approach. This study aims to develop a serious game-based cognitive rehabilitation system tailored for patients with brain injury. METHODS: The study included four stages. Initially, the requirements were analyzed through focus groups. Then the system structure and game content were discussed and was agreed as a conceptual model. In second stage, the system design was drawn using various modeling diagrams. In third stage, a system prototype was developed using the Unity game engine and C# programming. Finally, a heuristic evaluation method was employed to assess usability. RESULTS: Based on the focus group meetings with seven participants, a conceptual model of the system structure and game content was designed. Game's interface was developed for both the therapist and patient versions. The focus groups determined a 2D casual gaming genre with a postman character and 10 missions on the smartphone platform. For example, in the first mission, the postman must move from mailboxes 1 to 10 and pick up the letters. This is according to Trail Making Test task. The 16 tasks in different subcategories of attention were selected to make these missions. The usability evaluation highlighted privacy, help and documentation, and aesthetic and minimalist design as the areas with the highest percentage of problems. CONCLUSIONS: Cognitive rehabilitation is vital in facilitating patients' faster return to daily routines and enhancing their quality-of-life following brain injury. Incorporating a game-based system provides patients with increased motivation to engage in various cognitive exercises. Additionally, continuous monitoring by specialists ensures effective patient management. The game-based system offers different game stages to strengthen and rehabilitate attention in patients with brain injury. In the next step, the clinical effects of this system will be evaluated.

Isolation and evaluation of the efficacy of bacteriophages against multidrug-resistant (MDR), methicillin-resistant (MRSA) and biofilm-producing strains of Staphylococcus aureus recovered from bovine mastitis.

BACKGROUND: Staphylococcus aureus (S. aureus) is one of the major causes of bovine mastitis with significant economic losses around the worldwide. The emergence of multidrug-resistant (MDR), methicillin-resistant (MRSA) and biofilm-producing strains of S. aureus challenges the treatment strategies based on the antibiotic application. Today, alternative or combinational treatment options such as bacteriophage application has received much attention. The goal of the present study was to focus on isolation and evaluation of the efficacy of bacteriophages with specific lytic activity against S. aureus strains with low cure rates (MDR, MRSA and biofilm-producing strains). RESULTS: In the present study, two phages belonging to the Podoviridae family with specific lytic activity against S. aureus were isolated from the sewage of dairy farms and designated as Staphylococcus phage M8 and Staphylococcus phage B4. Latent period and burst size for Staphylococcus phage M8 (70 min, 72 PFU/cell) and Staphylococcus phage B4 (30 min, 447 PFU/cell) were also defined. Our results revealed the susceptibility of MDR (4/20; 20%), MRSA (4/13; 30.8%) and biofilm-producing (1/10; 10%) strains to Staphylococcus phage M8. Moreover, one biofilm-producing strain (1/10; 10%) was susceptible to Staphylococcus phage B4. Furthermore, both phages kept their lytic activity in milk. They reduced the S. aureus population by about 3 logs in cultured milk after 8 h of incubation. CONCLUSION: In conclusion, it seems that both phages had the potential to serve as biological control agents alone or in combination with other agents such as antibiotics against infections induced by S. aureus. However, further studies are needed to investigate the efficacy of these phages in vivo.

Boswellia serrata extract shows cognitive benefits in a double-blind, randomized, placebo-controlled pilot clinical trial in individuals who suffered traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury. METHOD: We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests. RESULT: The current study showed significant (p < 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI.

Lessons from COVID-19 pandemic: Clinical experiences on telemedicine in patients with dementia in Iran.

BACKGROUND: One of the impacts of COVID-19 pandemic on health system has been increasing the burden on the patients with dementia and their families. Telemedicine has shown to be a solution for this vulnerable group and can be used for cognitive assessment, medication adjustment, patient referral, reduces the travel time, cost and caregiver burden. Despite the challenges in acceptance for this novel technology in the elderly 1, it can reduce the burden of disease and increase access to specialised services. All these alongside neurologic visit could be provided with a telephone hotline or preferably video-platform tele-visit.2 However, barriers to develop telemedicine include a lack of broadband internet access and the need for insurance coverage.3 The American Academy of Neurology has been developed a comprehensive guideline to implement the tele-visit approach in the COVID-19 crisis with a special approach to neurological examination limitations in the patients.4 Numerous studies evaluated this approach to assess patients including dementia.5 Overall, the patients, caregivers, and the neurologists reported a high satisfaction rate.6 Yaadmaan Institution for Brain, Cognition and Memory Studies with a multidisciplinary team including cognitive neurologist, psychiatrist, psychologist, geriatrician, and clinical pharmacist is the first private referral center for cognitive disorders in Iran. After starting quarantine and tight restrictions and because of too many families who were seeking help for their patients via Yaadmaan helpline, we decided to start Telemedicine method. The approach and compatible examinations have been shown in Table 2 and 3 respectively. In addition, we defined a list of serious states to avoid Telemedicine for patients referal to the hospital in Table 4. Based on our one-year experiences, it seems there are promising results in-terms of feasibility, acceptability and convenience for the patient, caregiver and physician. However, due to the emergence of this pandemic, Telemedicine and its crucial role in Iran has not yet been identified in the insurance and health system appropriately. Even though Telemedicine was started as a practical and urgent solution against COVID-19 restrictions, it is necessary to be evaluated as an alternative method for clinical evaluations of the patients with dementia in Iran in the future.

Comparison of blood lipid-lowering effects of olive oil and other plant oils: A systematic review and meta-analysis of 27 randomized placebo-controlled clinical trials.

Objective: We aim to report a systematic review and meta-analysis of randomized controlled trials (RCTs) on effects of olive oil consumption compared with other plant oils on blood lipids. Methods: PubMed, web of science, Scopus, ProQuest, and Embase were systematically searched until September 2017, with no age, language and design restrictions. Weighed mean difference (WMD) and 95% confidence interval (CI) were expressed as effect size. Sensitivity analyses and pre specified subgroup was conducted to evaluate potential heterogeneity. Meta-regression analyses were performed to investigate association between blood lipid-lowering effects of olive oil and duration of treatment. Results: Twenty-seven trials, comprising 1089 participants met the eligibility criteria. Results of this study showed that compared to other plant oils, high-density lipoprotein level increased significantly more for OO (1.37 mg/dl: 95% CI: 0.4, 2.36). Also OO consumption reduced total cholesterol (TC) (6.27 mg/dl, 95% CI: 2.8, 10.6), Low-density lipoprotein (LDL-c) (4.2 mg/dl, 95% CI: 1.4, 7.01), and triglyceride (TG) (4.31 mg/dl, 95% CI: 0.5, 8.12) significantly less than other plant oils. There were no significant effects on Apo lipoprotein A1 and Apo lipoprotein B. Conclusion: This meta-analysis suggested that OO consumption decreased serum TC, LDL-c, and TG less but increased HDL-c more than other plant oils.

Effects of Canola Oil Consumption on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

Hyperlipidemia is a well- known risk factor of cardiovascular disease. A healthy diet containing vegetable oils such as canola oil (CO) may help to reduce serum lipids. This study aimed to quantify the effects of CO on lipid parameters using a systematic review and meta-analysis of randomized controlled trials. PubMed, Web of Science, Scopus, ProQuest, and Embase were systematically searched until December 2017, with no time and design restrictions. Also, a manual search was performed to find extra relevant articles. Lipid parameters including total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were entered the meta-analysis. Weighed mean difference (WMD) and 95% confidence interval (CI) were stated as the effect size. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity. Twenty-seven trials, comprising 1359 participants, met the eligibility criteria. Results of this study showed that CO consumption significantly reduced TC (-7.24 mg/dl, 95% CI, -12.1 to -2.7), and LDL (-6.4 mg/dl, 95% CI, -10.8 to -2), although it had no effects on HDL, TG, Apo B, and Apo A1. Effects of CO on TC and LDL significantly decreased after CO consumption in subgroups of >50 years of age participants and >30 intervention duration subgroup. Moreover, CO decreased LDL and TC compared to sunflower oil and saturated fat. This meta-analysis suggested that CO consumption improves serum TC and LDL, which could postpone heart disease progression. Key Teaching Points CO consumption could decrease serum TC and LDL, although it had no effects on other blood lipids. There was an overall significant effect of canola oil on TC and LDL compared to sunflower oil and saturated fats. CO could have beneficial effects on serum TC and LDL just when consumed longer than 30 days. CO consumption improved lipid profiles in participants older than 50 years.

Push-out bond strength of calcium-silicate cements following Er:YAG and diode laser irradiation of root dentin.

This study aimed to compare the effects of diode and Er:YAG laser irradiation of root dentin on push-out bond strength of mineral trioxide aggregate (MTA) and calcium-enriched mixture (CEM) cements. An in vitro experimental study was conducted on 90 dentin discs, cut out of freshly extracted human teeth. The discs were instrumented to obtain 1.3-mm lumen diameter. Then, they were randomly divided into six groups (n = 15). Groups 1 and 4 subjected to diode laser (Wiser, Doctor Smile, Italy) (980 nm, 1 W, continuous mode) for 10 s and filled with MTA and CEM cements. Groups 2 and 5 subjected to Er:YAG laser (Deka, Italy) (2940 nm, 1 W, 10 Hz, 230 µs) for 10 s and filled with MTA and CEM cements. Groups 3 and 6 (control groups) were filled with MTA and CEM cements without laser irradiation. After 7 days, push-out bond strength test was performed using a universal testing machine in order to evaluate the adhesion of the biomaterials to dentin. The samples were evaluated under a light microscope at × 40 magnification to determine the mode of fracture. Data were analyzed using two-way ANOVA. The highest push-out bond strength (8.76 ± 3.62 MPa) was noted in group 1 (diode/MTA), which was significantly higher than the other groups (P < 0.001). The lowest bond strength (2.61 ± 0.81) was noted in group 6 (control/CEM). Diode laser significantly increased the bond strength of both cements (P < 0.05), but Er:YAG laser irradiation only increased the bond strength of CEM and had no significant effect on MTA (P = 0.603). The bond strength of MTA control group was higher than that of CEM control group (P = 0.001). Push-out bond strength of endodontic cements can be affected by dentin conditioning with diode 980 nm and Er:YAG laser. Nine hundred eighty-nanometer diode laser irradiation is recommended to increase the bond strength of endodontic cements particularly the CEM cement to dentin.

Publication bias in otorhinolaryngology meta-analyses in 2021.

INTRODUCTION: One concern in meta-analyses is the presence of publication bias (PB) which leads to the dissemination of inflated results. In this study, we assessed how much the meta-analyses in the field of otorhinolaryngology in 2021 evaluated the presence of PB. METHODS: Six of the most influential journals in the field were selected. A search was conducted, and data were extracted from the included studies. In cases where PB was not assessed by the authors, we evaluated the risk of its presence by designing funnel plots and performing statistical tests. RESULTS: Seventy-five systematic reviews were included. Fifty-one percent of them used at least one method for assessing the risk of PB, with the visual inspection of a funnel plot being the most frequent method used. Twenty-nine percent of the studies reported a high risk of PB presence. We replicated the results of 11 meta-analyses that did not assess the risk of PB and found that 63.6% were at high risk. We also found that a considerable proportion of the systematic reviews that found a high risk of PB did not take it into consideration when making conclusions and discussing their results. DISCUSSION: Our results indicate that systematic reviews published in some of the most influential journals in the field do not implement enough measures in their search strategies to reduce the risk of PB, nor do they assess the risk of its presence or take the risk of its presence into consideration when inferring their results.

Rapid eye movement sleep behavior disorder and its relation to Parkinson's disease: The potential of graph measures as brain biomarkers to identify the underlying physiopathology of the disorder.

Rapid eye movement behavior disorder (RBD) is a parasomnia characterized by the loss of skeletal muscle atonia during the rapid eye movement (REM) sleep phase. On the other hand, idiopathic RDB (iRBD) is considered the prelude of the various α-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. Consequently, over 40% of patients eventually develop PD. Recent neuroimaging studies utilizing structural magnetic resonance imaging (s-MRI), diffusion-weighted imaging (DWI), and functional magnetic resonance imaging (fMRI) with graph theoretical analysis have demonstrated that patients with iRBD and Parkinson's disease have extensive brain abnormalities. Thus, it is crucial to identify new biomarkers that aid in determining the underlying physiopathology of iRBD group. This review was conducted systematically on the included full-text articles of s-MRI, DWI, and fMRI studies using graph theoretical analysis on patients with iRBD, per the procedures recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature search was conducted through the PubMed and Google scholar databases concentrating on studies from September to January 2022. Based on the three perspectives of integration, segregation, and centrality, the reviewed articles demonstrated that iRBD is associated with segregation disorders in frontal and limbic brain regions. Moreover, this study highlighted the need for additional longitudinal and multicenter studies to better understand the potential of graph metrics as brain biomarkers for identifying the underlying physiopathology of iRBD group.

Evaluating the Effects of Rivastigmine on Decision-Making in Patients with Mild Cognitive Impairment by Cambridge Neuropsychological Test Automated Battery (CANTAB); A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Decision-making is a complex process, and most studies showed that patients with mild cognitive impairment (MCI) make worse decisions than healthy people. Objectives: This study aims to evaluate the effect of rivastigmine on the decision-making of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests. Methods: The study was conducted at the Roozbeh Hospital neurology clinic, and 30 patients with mild cognitive impairment over 40 years old were randomly recruited to receive rivastigmine or placebo twice daily for 12 weeks. The initial dose of rivastigmine or placebo was 1.5 mg twice daily and was increased to 3 mg twice daily per patient compliance. A CANTAB test was conducted before and following the intervention. Results: The mean age of patients in the rivastigmine group was 58.93 ± 10.88, and in the placebo group was 59.33 ± 10.34. The median MMSE (Mini-Mental State Examination) was 26 (IQR = 25 - 26) in both groups. Patients in the rivastigmine group showed significant differences in all subgroup tests of CGT, IST, and SST except in risk adjustment in the CGT test, discrimination in the IST test, and median correct RT on the go trial and SSRT in the SST test. The most commonly reported adverse effects were gastrointestinal complications. Conclusions: According to the results, rivastigmine significantly improved the primary decision-making outcomes in comparison with placebo.

Effects of remote combine exercise-music training on physical and cognitive performance in patients with Alzheimer's disease: a randomized controlled trial.

Introduction: This study aimed to investigate the effects of combined remote music and exercise training on the cognitive, psychological, and physical function of patients with Alzheimer's disease (AD). Methods: Forty-one AD patients were randomly allocated to three groups, including control (C), training (T), and training with music (TM) groups. Participants were evaluated by cognitive and performance test batteries before and after the interventions. Both experimental groups performed 36 remote workouts in 3 months online via WhatsApp video call individually with the trainer. Training included simple and varied movements of all physical indicators. The number of sets began with two sets and progressively increased to one set every month, 5-10 repetitions per set. The overload was applied by reducing the break between sets every week. The TM group performed the same exercises while listening to Mozart and traditional Iranian songs. Results: We observed a significant main, group, time, and interaction effect on Romberg (ηp2:0.72), 30 s chair sit and stand (ηp2:0.75), and walking on steppe test (ηp2:0.63). Furthermore, there was a significant main time and interaction effect on push-ups (ηp2:0.43), sit and reach (ηp2:0.64), and MMSE (ηp2:0.76). In all variables, two experimental groups demonstrated substantial improvements than the C group (p < 0.01). In addition, the TM group (27.8%) showed a significant improvement compared to the C group (-6.4%) and the T group (12.2%) in MMSE. Conclusion: Combined remote training with listening to music as adjuvant treatment is an appropriate item to improve the cognitive and physical performance of Alzheimer's patients, especially during the COVID-19 pandemic.

Therapeutic and prophylactic effects of radiation therapy in the management of recurrent granulation tissue induced tracheal stenosis: a review on the role of Endobronchial brachytherapy and external beam radiation therapy.

PURPOSE: Granulation tissue-induced tracheal stenosis (mainly secondary to intubation or lung transplantation) is one of the most common etiologies of benign airway obstructions. Recurrence rates after standard treatment options (surgical resection and/or endobronchial interventions) can inadvertently worsen the stricture through the stimulation of more granulation tissue generation (via increased fibroblast activity and roliferation). Low-dose radiotherapy could be a promising tool to prevent granulation tissue formation after surgery and/or endobronchial interventions regarding its established role in the treatment of keloids or hypertrophic scars, two benign diseases with similar a pathophysiology to tracheal stenosis. This study reviews case reports and small series that used endobronchial brachytherapy (EBBT) or external beam radiotherapy (EBRT) for the management of refractory granulation tissue-induced tracheal stenosis after surgery and/or endobronchial interventions. METHODS AND MATERIALS: Case reports and series (published up to October 2022) that reported outcomes of patients with recurrent granulation tissue-induced tracheal stenosis (after surgery and/or endobronchial interventions) treated by EBBT or EBRT (in definitive or prophylactic settings) were eligible. RESULTS: Sixteen studies (EBBT: nine studies including 69 patients, EBRT: seven studies including 32 patients) were reviewed. The pooled success rate across all studies was 74% and 97% for EBBT and EBRT, respectively. CONCLUSIONS: Radiation therapy appears to be effective in the management of selected patients with recurrent/refractory tracheal stenosis. Response to this treatment is usually good, but further studies with a larger number of patients and long-term followup are necessary to determine the optimal technique, dose, and timing of radiation therapy, late complications, the durability of response, and criteria for patient selection.

Ginkgo biloba Efficacy in the Treatment of Drug-Induced Parkinsonism: A Randomized Clinical Trial.

Background: Drug-induced parkinsonism (DIP) is one of the most common movement disorders in approximately 20 - 35% of patients on antipsychotic medications. Managing the symptoms of DIP is challenging due to the limited number of potentially effective medications. On the other hand, this restricted possible treatment could have numerous side effects that ultimately result in patients stopping the medication all at once. The neuroprotective property of Ginkgo biloba extract (EGb) emerged as an effective commodity for the additional treatment of psychiatric disorders. Objectives: This study aimed to evaluate the efficacy of EGb in psychiatric patients with symptoms of DIP. Methods: A sample of 63 patients who met the inclusion criteria were recruited and randomly assigned to control and experimental groups. Both groups were followed for 3 months. One group received 80 mg of G. biloba three times a day, and the control group received a placebo. The patients were evaluated using the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment. Results: Ginkgo could change the intensity of rest tremors, the severity of motor symptoms, rigidity, and bradykinesia. Ginkgo biloba might alleviate the severity of parkinsonism and motor symptoms and could lead to changes in the two components of working memory and short-term memory. Conclusions: Ginkgo biloba extract can be used as an effective and safe treatment in the management of DIP, whether in patients diagnosed with psychotic disorders or mood disorders.

Effective Connectivity Evaluation of Resting-State Brain Networks in Alzheimer's Disease, Amnestic Mild Cognitive Impairment, and Normal Aging: An Exploratory Study.

(1) Background: Alzheimer's disease (AD) is a neurodegenerative disease with a high prevalence. Despite the cognitive tests to diagnose AD, there are pitfalls in early diagnosis. Brain deposition of pathological markers of AD can affect the direction and intensity of the signaling. The study of effective connectivity allows the evaluation of intensity flow and signaling pathways in functional regions, even in the early stage, known as amnestic mild cognitive impairment (aMCI). (2) Methods: 16 aMCI, 13 AD, and 14 normal subjects were scanned using resting-state fMRI and T1-weighted protocols. After data pre-processing, the signal of the predefined nodes was extracted, and spectral dynamic causal modeling analysis (spDCM) was constructed. Afterward, the mean and standard deviation of the Jacobin matrix of each subject describing effective connectivity was calculated and compared. (3) Results: The maps of effective connectivity in the brain networks of the three groups were different, and the direction and strength of the causal effect with the progression of the disease showed substantial changes. (4) Conclusions: Impaired information flow in the resting-state networks of the aMCI and AD groups was found versus normal groups. Effective connectivity can serve as a potential marker of Alzheimer's pathophysiology, even in the early stages of the disease.

Antiviral Potential of Melissa officinalis L.: A Literature Review.

The use of synthetic drugs has increased in recent years; however, herbal medicine is yet more trusted among a huge population worldwide; This could be due to minimal side effects, affordable prices, and traditional beliefs. Lemongrass (Melissa officinalis) has been widely used for reducing stress and anxiety, increasing appetite and sleep, reducing pain, healing wounds, and treating poisonous insect bites and bee stings for a long time. Today, research has shown that this plant can also fight viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV) through various mechanisms such as inhibiting HSV-1 from binding to host cell, inhibiting HSV-1 replication during the post-adsorption or inhibiting main protease and spike protein of SARS-CoV-2, furthermore, be effective in treating related diseases. This Review investigated the antiviral properties of Melissa officinalis and its effect on viral diseases. More in vitro and in vivo studies are needed to determine Melissa officinaliss underlying mechanism, and more randomized controlled trials should be done to identify its effect in humans. Also, due to the usefulness and lack of side effects, it can be used more as a complementary medicine.

Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial.

AIM: To test if opium tincture (OT) was non-inferior to methadone in retaining participants in opioid agonist treatment (OAT). DESIGN: A Phase III, multi-centre, parallel-group, non-inferiority, double-blind randomized controlled trial with an allocation ratio of 1:1. Participants were provided treatment and followed for a period of 85 days. SETTING: Four OAT clinics in Iran. PARTICIPANTS: Two hundred and four participants with opioid use disorder [mean age (standard deviation) = 37.4 (9.3); female 11.3%] recruited between July 2017 and January 2018. INTERVENTIONS: Participants were assigned to either OT (102) or methadone (102) using a patient-centred flexible dosing strategy. MEASUREMENTS: Treatment retention over 85 days was the primary outcome. Self-reported opioid use outside treatment and occurrence of adverse events (AEs) were the secondary outcomes. FINDINGS: Remaining in treatment at the end of the follow-up were 68.6% in the methadone arm and 59.8% in the OT arm. The relative retention rate of methadone to OT was 1.15 (0.97, 1.36) in both intent-to-treat and per-protocol analyses; non-inferiority was not supported statistically, as the upper bound of the confidence interval exceeded our pre-specified non-inferiority margin (1.25). Opioid use outside treatment was reported by 30.3% of OT (n = 152) and 49.4% of methadone (n = 168) patients, a difference in proportions of -19%: 90% confidence interval (-28%, -10%). The total count of AEs in the OT arm (22 among nine individuals) was significantly higher (P = 0.04) than that in the methadone arm (three among two individuals). Nausea was the most common side effect. CONCLUSION: While this study could not conclude the non-inferiority of opium tincture (OT) to methadone for retaining patients in opioid agonist treatment, OT retained 60% of participants to end of follow-up (85 days) and was superior to methadone in reducing self-reported opioid use outside treatment.

A Systematic Review on Serious Games in Attention Rehabilitation and Their Effects.

Attention is a basic and main mental task and can play an important role in the functioning of other brain abilities such as intelligence, memory, learning, and perception, and its deficit occurs in 80% of patients with traumatic brain injury. The use of game-based tools for rehabilitation is rapidly expanding. Cognitive rehabilitation via video games is an emerging hot topic in cognitive science. Serious games serve a specific purpose in addition to entertainment. They can be more engaging than exercises since they replace reward and motivation systems with real-world motivations as a complement for rehabilitation activities. This study was aimed at identifying and categorizing serious computer games used for attention rehabilitation and evaluating their effects. Six electronic databases (Scopus, PubMed, ISI, Embase, IEEE, and Cochrane) were searched in August 2021. The search strategy consisted of three main concepts of "serious game", "cognitive deficits", and "cognitive rehabilitation". The inclusion criteria were (1) journal articles, (2) English language, (3) being published in the last 10 years, (4) human participants, and (5) game-based intervention. In the 30 included studies, 22 unique games were utilized for attention rehabilitation. Lumosity (20%), Brain Age (Dr. Kawashima's Brain Training) (10%), and MoHRS (6.66%) were the most common games among the studies. There were (57%) casual, (23%) action, (10%) simulation, and (10%) multiple genres. Of the 47 tools used in the studies, 5 utilized cross-modal oddball attention tasks, 4 utilized game performance, 3 utilized the paced auditory serial additional test (PASAT), and the rest employed other tools. A total of 73 outcome measures were related to attention, 42 measures did not have significant results, 30 were significantly improved, 1 was significantly deteriorated, and 4 articles did not have any specific measures for attention evaluation. Thus, the results revealed the positive effect of serious games on attention. However, issues such as absence of scientific teams, the variety of the disorders that cause defects, the variety of criteria, differences in measurements, lack of long-term follow-up, insufficient RCT studies, and small sample sizes should be considered when designing, developing, and using game-based systems to prevent bias.

Relationship Between Psychological Impacts of COVID-19 and Loneliness in Patients With Dementia: A Cross-Sectional Study From Iran.

Objectives: Although the COVID-19 pandemic has affected people all around the world, the elderly is at a higher risk of suffering from its consequences. One of the serious concerns is developing loneliness and post-traumatic stress symptoms, which may contribute to cognitive decline at older ages. This study aimed to examine the psychological responses and loneliness in elderly patients diagnosed with dementia. Methods: Twenty-one patients diagnosed with dementia, with ages older than 40, and 19 caregivers were enrolled in the study. The patients have undergone a comprehensive neuropsychiatric interview and were assessed with De Jong Gierveld Scale for loneliness and Impact of Event Scale-Revised (IES-R). The severity of dementia was assessed by Functional Assessment Staging Tool (FAST Scale) and the Montreal Cognitive Assessment (MoCA). Results: No significant difference was seen in patients and caregivers in the IES-R and loneliness scales. A higher level of avoidance and social and total loneliness were seen in higher FAST levels (p-value: 0.046). There was a negatively significant correlation between MoCA score and avoidance. Hyperarousal was significantly correlated with emotional loneliness in patients. Conclusion: We found a direct relationship between cognitive decline and the psychological impacts of COVID-19. Our results highlight the need for more comprehensive studies to further investigate the influence of the pandemic on the worsening of cognitive impairment and loneliness in patients with dementia.