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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Predictors of poor cosmesis in breast cancer patients treated with adjuvant whole breast radiation therapy plus high-dose-rate interstitial brachytherapy boost after breast conservation surgery.

Purpose: To identify patient, tumor, and treatment-related factors, which predict cosmesis in breast cancer survivors treated with adjuvant whole breast irradiation (WBI) plus high-dose-rate (HDR) multicatheter interstitial brachytherapy (MIBT) boost after breast conservation surgery. Material and methods: At least 12 months after completion of radiotherapy, cosmetic outcomes were measured both objectively with BCCT.core software (using a front view digital photograph), and subjectively according to Harvard's criteria. MIBT dose fractionation regimen was 13.6 Gy/4 fractions (bid). To evaluate the correlation between cosmetic scores and dose-volume histogram (DVH) parameters, WBI and MIBT plans were retrospectively analyzed, and ipsilateral skin and breast biologically equivalent dosimetric indices were recorded (α/ß = 3 Gy). A multivariate ordinal logistic regression model was used for statistical analysis. Results: Twenty-eight consecutive patients were enrolled into this study. The median time from completion of radiation therapy to cosmesis scoring was 18 months. In evaluation with BCCT.core software, no patient was scored as excellent. Cosmesis was good in 18%, fair in 50%, and poor in 32% of patients. According to Harvard's scale, 10.5% of patients had excellent cosmesis, and 43%, 28.5%, and 18% of patients had good, fair, and poor scores, respectively. In univariate analysis, patients with higher absolute MIBT V29Gy (cc), those treated with irradiation of regional lymphatics (odds ratio ≈ 5), and patients with larger breast volumes had statistically significant lower Harvard's scores. In the multivariate model, none of the mentioned factors remained statistically significant, except for a trend for poorer cosmesis in patients with higher absolute MIBT V29Gy (p-value = 0.066). Conclusions: Based on the results of this study, MIBT breast V29Gy, regional nodal irradiation, and larger breast volumes are the potential factors, which could predict cosmesis.

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.

Psychiatric Onset Alexander Disease: An Important Challenge in Neuropsychiatric Diagnosis: A Case Report.

Introduction: Alexander disease is a heterogeneous group of diseases with various manifestations based on the age of disease onset. This rare leukodystrophy syndrome with mutations in the GFAP gene could present with developmental delay and seizure in the infantile form to ataxia and bulbar palsy in adulthood. However, psychiatric symptoms are not well-defined and are usually evaluated after disease diagnosis, not before disease investigations. Case Report: Our patient is a 52-year-old Iranian woman with a history of depression since 17 years ago, a suicidal attempt two years ago, and ingestion of a large amount of opium with the intention of suicide 2 months ago. She was presented with disorientation and probably a delirious state in the last interview. Eventually, in comprehensive investigations, white matter hyperintensity in MRI and leukodystrophy was diagnosed to determine the cause of these changes, we did a gene study, found whole exon deletion of the GFAP gene, and made a diagnosis of late-onset Alexander disease. Conclusion: Neurological-onset manifestation of Alexander disease, specifically late-onset form, is the most common clinical picture of disease and was seen in about 90% of patients, but psychiatric symptoms are not well-known, and psychiatric-onset disease was not described yet. Various gene mutations were described in late-onset Alexander disease; however, the large whole exon deletion which was revealed in our patient is a novel mutation and significantly needs to be explored. Here authors describe a late-onset Alexander disease with psychiatric-onset symptoms and novel large exon deletion in the GFAP gene. Highlights: Alexander disease is a rare heterogeneous disorder that could have various symptoms of the central nervous system involvement.The whole-exons deletion of the GFAP gene in an adult patient with features of Alexander disease is the first Gene mutation that was revealed in this case.Psychiatric onset Alexander disease is the one differential diagnosis in the patients with atypical psychiatric symptoms combined with soft neurological signs.Neurologic consultation and appropriate imaging and laboratory procedures could help early diagnosis and potential treatment. Plain Language Summary: Patients with atypical psychiatric symptoms are usually visited more times in the year without any significant benefit. They receive numerous medications and encounter significant complications due to mentioned polypharmacy. However, genetic, metabolic, or neurological causes could be considered in some treatment-resistant cases. We described the rare genetic disorder(Late-Onset Alexander disease) in the Iranian woman with atypical and treatment-resistant depression with suicidal attempts. We proposed holistic assessment in the patients with psychiatric symptoms which have atypical course or response to treatment or are accompanied by neurological and cognitive symptoms.

The comparison of transforming growth factor beta-1 serum levels in early-stage breast cancer patients treated with external beam whole breast irradiation plus boost versus interstitial brachytherapy accelerated partial breast irradiation.

PURPOSE: Transforming growth factor beta-1 (TGF-ß1) is a profibrotic cytokine used as an early biomarker to develop radiation-induced fibrosis (RIF). This study aimed to compare TGF-ß1 serum levels in early-stage breast cancer patients treated with whole-breast radiation therapy (WBRT) plus boost versus accelerated partial breast irradiation (APBI) using multicatheter interstitial brachytherapy. METHODS AND MATERIALS: This clinical trial study was conducted on 20 women with early-stage breast cancer after breast-conserving surgery candidate for adjuvant radiotherapy in Golestan hospital, Ahvaz, in 2021. In one group APBI with high-dose-rate brachytherapy (n = 10), the other group WBRT with external beam radiation plus boost (n = 10) was performed. Serum level of TGF-ß1 was evaluated before radiotherapy, immediately after the end of radiotherapy and three months after the end of radiotherapy by Enzyme-linked immunosorbent assay technique (ELISA). RESULTS: Median serum TGF-ß1 level before radiotherapy was not significantly different between the two groups (p = 0.971). In both APBI and WBRT groups, serum TGF-ß1 levels significantly decreased immediately after radiotherapy compared to before treatment (p = 0.005 and p = 0.007, respectively); But three months after radiotherapy, serum TGF-ß1 levels increased significantly in the WBRT group (40.50 to 77.41 pg/mL; p = 0.017), while no significant change was observed in the APBI group (24.75 to 30.50 pg/mL; p = 0.332). CONCLUSIONS: Higher TGF-ß1 values in the WBRT group after radiotherapy can be used as an early and vital biomarker in this treatment, and this data may corroborate links between TGF-beta1 and fibrosis and fibrosis rates between APBI and WBRT; It also shows the preference for using the brachytherapy technique in this group of patients. However, due to the small number of samples, definitive conclusions require further prospective studies.

Brachytherapy outcome modeling in cervical cancer patients: A predictive machine learning study on patient-specific clinical, physical and dosimetric parameters.

PURPOSE: To predict clinical response in locally advanced cervical cancer (LACC) patients by a combination of measures, including clinical and brachytherapy parameters and several machine learning (ML) approaches. METHODS: Brachytherapy features such as insertion approaches, source metrics, dosimetric, and clinical measures were used for modeling. Four different ML approaches, including LASSO, Ridge, support vector machine (SVM), and Random Forest (RF), were applied to extracted measures for model development alone or in combination. Model performance was evaluated using the area under the curve (AUC) of receiver operating characteristics curve, sensitivity, specificity, and accuracy. Our results were compared with a reference model developed by simple logistic regression applied to three distinct clinical features identified by previous papers. RESULTS: One hundred eleven LACC patients were included. Nine data sets were obtained based on the features, and 36 predictive models were built. In terms of AUC, the model developed using RF applied to dosimetric, physical, and total BT sessions features were found as the most predictive [AUC; 0.82 (0.95 confidence interval (CI); 0.79 -0.93), sensitivity; 0.79, specificity; 0.76, and accuracy; 0.77]. The AUC (0.95 CI), sensitivity, specificity, and accuracy for the reference model were found as 0.56 (0.52 ...0.68), 0.51, 0.51, and 0.48, respectively. Most RF models had significantly better performance than the reference model (Bonferroni corrected p-value < 0.0014). CONCLUSION: Brachytherapy response can be predicted using dosimetric and physical parameters extracted from treatment parameters. Machine learning algorithms, including Random Forest, could play a critical role in such predictive modeling.

Different Protocols of Combined Application of Photobiomodulation In Vitro and In Vivo Plus Adipose-Derived Stem Cells Improve the Healing of Bones in Critical Size Defects in Rat Models.

Introduction: Long bone segmental deficiencies are challenging complications to treat. Hereby, the effects of the scaffold derived from the human demineralized bone matrix (hDBMS) plus human adipose stem cells (hADSs) plus photobiomodulation (PBM) (in vitro and or in vivo) on the catabolic step of femoral bone repair in rats with critical size femoral defects (CDFDs) were evaluated with stereology and high stress load (HSL) assessment methods. Methods: hADSs were exposed to PBM in vitro; then, the mixed influences of hDBMS+hADS+PBM on CSFDs were evaluated. CSFDs were made on both femurs; then hDBMSs were engrafted into both CSFDs of all rats. There were 6 groups (G)s: G1 was the control; in G2 (hADS), hADSs only were engrafted into hDBMS of CSFD; in G3 (PBM) only PBM therapy for CSFD was provided; in G4 (hADS+PBM in vivo), seeded hADSs on hDBMS of CSFDs were radiated with a laser in vivo; in G5 (hADSs+PBM under in vitro condition), hADSs in a culture system were radiated with a laser, then transferred on hDBMS of CSFDs; and in G6 (hADS+PBM in conditions of in vivo and in vitro), laser-exposed hADSs were transplanted on hDBMS of CSFDs, and then CSFDs were exposed to a laser in vivo. Results: Groups 4, 5, and 6 meaningfully improved HSLs of CSFD in comparison with groups 3, 1, and 2 (all, P=0.001). HSL of G5 was significantly more than G4 and G6 (both, P=0.000). Gs 6 and 4 significantly increased new bone volumes of CSFD compared to Gs 2 (all, P=0.000) and 1 (P=0.001 & P=0.003 respectively). HSL of G 1 was significantly lower than G5 (P=0.026). Conclusion: HSLs of CSFD in rats that received treatments of hDBMS plus hADS plus PBM were significantly higher than treatments with hADS and PBM alone and control groups.

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.

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.