Circulating brain-derived neurotrophic factor as a potential biomarker in stroke: a systematic review and meta-analysis.

BACKGROUND: Stroke, an acute cerebrovascular event, is a leading cause of disability, placing a significant psycho-socioeconomic burden worldwide. The adaptation and reorganization process following any neuronal damage is regarded as neuroplasticity. Among many factors believed to attribute to this process, Brain-derived Neurotrophic Factor (BDNF) is a neurotrophin coordinating neuroplasticity after various neurological disorders such as stroke. METHODS: We conducted a systematic search in the main electronic medical databases in January 2021. Primarily we want to compare BDNF levels between patients with stroke and healthy controls (HC). Additional aims included investigation of (1) longitudinal changes in the BDNF levels post-stroke, (2) effects of physical training, (3) repeated transcranial magnetic stimulation (rTMS), and presence of depression on BDNF levels in patients with stroke. RESULTS: Among 6243 reviewed records from PubMed, Web of Science, and Scopus, 62 studies were eligible for inclusion in our systematic review. Subjects with stroke, n = 1856, showed lower BDNF levels compared to HC, n = 1191 (SMD [95%CI] = - 1.04 [- 1.49 to - 0.58]). No significant difference was detected in the level of BDNF through time points past stroke. BDNF levels were lower in the patients with depression compared to non-depressed subjects (SMD [95%CI] = - 0.60 [- 1.10 to - 0.10]). Physical training had an immediate positive effect on the BDNF levels and not statistically significant effect in the long term; SMD [95%CI] = 0.49 [0.09 to 0.88]) and SMD [95%CI] = 0.02 [- 0.43 to 0.47]). Lastly, rTMS showed no effect on the level of BDNF with 0.00 SMD. CONCLUSIONS: Our study confirms that stroke significantly decreases the level of BDNF in various domains such as cognition, affect, and motor function. As BDNF is the major representative of neuroplasticity within nervous system, it is believed that stroke has a significant impact on the CNS regeneration, which is permanent if left untreated. This effect is intensified with coexisting conditions such as depression which further decrease the BDNF level but the net impact yet needs to be discovered. We also conclude that exercise and some interventions such as different medications could effectively reverse the damage but further studies are crucial to reach the exact modality and dosage for their optimal effect.

The clinical significance of biliary findings in magnetic resonance enterography of patients with inflammatory bowel disease.

Purpose: Given the association of inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), we aimed to investigate the clinical relevance of abnormal hepatobiliary findings on magnetic resonance enterography (MRE) of IBD patients considering the risk of over- or underestimation of PSC at MRE. Material and methods: Using the MRE dataset of patients referring to a tertiary hospital and the National Registry of Crohn's and Colitis, 69 MREs, including 23 IBD-PSC, 23 IBD-without PSC, and 23 healthy controls (HC), were retrospectively reviewed by 2 experienced radiologists blinded to the clinical data, to evaluate hepatobiliary abnormalities. Sensitivity, specificity, and likelihood ratios were calculated. Results: Bile duct irregularities were the most common finding in the IBD-PSC group, with a frequency of 91%. Intra- and extrahepatic bile duct (IHBD and EHBD) irregularities were observed in 87% and 78% of PSC patients, respectively. Higher frequency of IHBD and EHBD wall thickening, bile duct dilation, EHBD stricture, and periportal oedema were observed in the IBD-PSC group. Peribiliary T2-weighted hyperintensities and contrast-enhancement were significantly more common in the IBD-PSC group than in the IBD and HC groups (48% and 35%, respectively) (p < 0.001). Detection of biliary irregularities on MRE had a specificity of 94% (95% CI: 82-99%), a sensitivity of 91% (95% CI: 72-99%), and a positive likelihood ratio of 14.0 (95% CI: 4.7-42.1) for the diagnosis of PSC. Conclusions: This study emphasizes the importance of assessing and reporting hepatobiliary abnormalities visible in the MRE of patients with IBD to avoid a delayed diagnosis of PSC.

Socialization During the COVID-19 Pandemic: The Role of Social and Scientific Networks During Social Distancing.

In the COVID-19 era, while we are encouraged to be physically far away from each other, social and scientific networking is needed more than ever. The dire consequences of social distancing can be diminished by social networking. Social media, a quintessential component of social networking, facilitates the dissemination of reliable information and fighting against misinformation by health authorities. Distance learning, telemedicine, and telehealth are among the most prominent applications of networking during this pandemic. Additionally, the COVID-19 pandemic highlights the importance of collaborative scientific efforts. In this chapter, we summarize the advantages of harnessing both social and scientific networking in minimizing the harms of this pandemic. We also discuss the extra collaborative measures we can take in our fight against COVID-19, particularly in the scientific field.

A novel VPS13B mutation in Cohen syndrome: a case report and review of literature.

BACKGROUND: Cohen syndrome, an autosomal recessive syndrome, is a rare syndrome with diverse clinical manifestations including failure to thrive, hypotonia, hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, neutropenia and a friendly character. It is associated with mutations of the vacuolar protein sorting 13 homolog B (VPS13B) gene, which is involved in the development of the ocular, hematological and central nervous systems. This gene encodes a transmembrane protein playing a crucial role in preserving the integrity of the Golgi complex. To date, more than 150 mutations of VPS13B have been reported in over 200 Cohen syndrome patients. Missense or nonsense mutations are the most common mutations. CASE PRESENTATION: A 4-year-old girl, born to consanguineous parents, was referred to the pediatric clinical immunology outpatient clinic for investigation of recurrent neutropenia with a history of recurrent infections in the past year. On physical examination, she had the characteristic facial features of Cohen syndrome, developmental delay and speech disorder. She had a cheerful disposition, and her mother gave a history of feeding difficulties in her first months of life. She did not present any ophthalmologic or cardiac abnormalities. Her lab results revealed moderate neutropenia. Serum IgG, IgM, IgA and IgE levels were normal. She fulfilled the clinical diagnostic criteria for Cohen syndrome. WES revealed a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49). Currently, she is not experiencing any severe problem, and she undergoes irregular medical treatment once her neutrophil count decreases under the normal limit. Her verbal and motor abilities have improved as a result of speech and occupational therapies. CONCLUSION: We reported a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49) in a 4-year-old girl with Cohen syndrome. Cohen syndrome should be considered in differential diagnosis of any child with intellectual disability and neutropenia.

Sulforaphane as an adjunctive treatment for irritability in children with autism spectrum disorder: A randomized, double-blind, placebo-controlled clinical trial.

AIM: Irritability related to autism spectrum disorder (ASD) complicates the management of ASD patients at home and in clinical settings. In this randomized, double-blind, placebo-controlled clinical trial, we aimed to investigate the beneficial effects of adjuvant treatment with risperidone and sulforaphane in alleviating the irritability of children with ASD. METHODS: Sixty drug-free patients aged 4-12 years were randomly assigned to one of two groups receiving risperidone plus sulforaphane or placebo. Risperidone was started with a daily dose of 0.25 mg in patients weighing <20 kg and 0.5 mg in those weighing ≥20 kg and increased stepwise to reach a maximum of 1 mg (<20 kg), 2.5 mg (20-45 kg), and 3.5 mg (>45 kg). Sulforaphane was administered at a daily dose of 50 µmol (≤45 kg) or 100 µmol (>45 kg). The participants were assessed with the Aberrant Behavior Checklist - Community Edition at baseline and at Weeks 5 and 10. RESULTS: Compared to the placebo group, ASD patients in the sulforaphane group showed greater improvements in Irritability score (primary outcome measure; P = 0.001) and Hyperactivity/Noncompliance score (secondary outcome measure; P = 0.015), and significant Time × Treatment effect for Irritability (P = 0.007) and Hyperactivity/Noncompliance (P = 0.008). However, no difference was seen in improvements in the other secondary measures: Lethargy/Social Interaction score, Stereotypic Behavior score, Inappropriate Speech score, and frequency of adverse events. CONCLUSION: Our results support the safety and efficacy of sulforaphane as an adjuvant to risperidone for improvement of irritability and hyperactivity symptoms in children with ASD.

Connecting the dots: An updated review of the role of autoimmunity in narcolepsy and emerging immunotherapeutic approaches.

BACKGROUND: Narcolepsy type 1 (NT1) is a chronic disorder characterized by pathological daytime sleepiness and cataplexy due to the disappearance of orexin immunoreactive neurons in the hypothalamus. Genetic and environmental factors point towards a potential role for inflammation and autoimmunity in the pathogenesis of the disease. This study aims to comprehensively review the latest evidence on the autoinflammatory mechanisms and immunomodulatory treatments aimed at suspected autoimmune pathways in NT1. METHODS: Recent relevant literature in the field of narcolepsy, its autoimmune hypothesis, and purposed immunomodulatory treatments were reviewed. RESULTS: Narcolepsy is strongly linked to specific HLA alleles and T-cell receptor polymorphisms. Furthermore, animal studies and autopsies have found infiltration of T cells in the hypothalamus, supporting T cell-mediated immunity. However, the role of autoantibodies has yet to be definitively established. Increased risk of NT1 after H1N1 infection and vaccination supports the autoimmune hypothesis, and the potential role of coronavirus disease 2019 and vaccination in triggering autoimmune neurodegeneration is a recent finding. Alterations in cytokine levels, gut microbiota, and microglial activation indicate a potential role for inflammation in the disease's development. Reports of using immunotherapies in NT1 patients are limited and inconsistent. Early treatment with IVIg, corticosteroids, plasmapheresis, and monoclonal antibodies has seldomly shown some potential benefits in some studies. CONCLUSION: The current body of literature supports that narcolepsy is an autoimmune disorder most likely caused by T-cell involvement. However, the potential for immunomodulatory treatments to reverse the autoinflammatory process remains understudied. Further clinical controlled trials may provide valuable insights into this area.

Nonalcoholic Fatty Liver Disease as a Potential Risk Factor for Cardiovascular Disease in Patients with Type 2 Diabetes: A Prospective Cohort Study.

Methods and Results: In this prospective cohort study, 1197 patients with type 2 diabetes (T2D) were divided into two groups (360 patients with NAFLD and 847 without NAFLD) and were followed for a median of 5 years for the incidence of CVD. Cox regression analysis was used to assess the association between NAFLD, liver enzyme level, aspartate aminotransferase to platelet ratio index (APRI), and the incidence risk of CVD and its subgroups (i.e., myocardial infarction, chronic heart disease, coronary artery bypass grafting, and percutaneous coronary intervention). There was a significant positive association between CVD incidence and NAFLD (HR = 1.488, 95% CI = 1.041-2.124, p value = 0.029). Although patients with NAFLD had higher levels of ALT and AST levels (p value = <0.001), there was no significant association between liver enzymes and the incidence risk of CVD when adjusted for different variables. Furthermore, NAFLD was associated with NAFLD APRI Q (2), APRI Q (3), and APRIQ (4) (1.365 (1.046-1.781), 1.623 (1.234-2.135), and 3.373 (2.509-4.536)), respectively. Conclusion: NAFLD increased the incidence risk of CVD in T2D. However, there was no association between liver enzymes (ALT, AST, ALK-P, and GGT) and a higher incidence risk of CVD in T2D when adjusted for confounding variables.

Infective Endocarditis in North Africa and the Middle East, 1990‒2019: Updates from the Global Burden of Disease Study 2019.

BACKGROUND: Infective endocarditis (IE), a severe and economically impactful condition, lacks substantial epidemiological data in the North Africa and Middle East (NAME) region. This study focused on analyzing the trends and burden of IE in NAME from 1990 to 2019, taking into account factors like age, gender, and socio-demographic index (SDI). METHODS: The Global Burden of Disease data from 1990 to 2019 was retrieved from the Institute for Health Metrics and Evaluation (IHME) website. RESULTS: Between 1990 and 2019, the age-standardized rates (ASR) for IE incidence increased by 59%, and prevalence and years lived with disability (YLDs) rose by 12% and 9%, respectively, while the ASRs for deaths, disability-adjusted life years (DALYs), and years of life lost (YLLs) saw reductions of 22%, 34%, and 34% in the NAME region. Death rates among children under five declined by 72%. Gender and the SDI did not significantly influence these changes. Saudi Arabia witnessed the most significant increase in ASR of IE incidence since 1990, while Turkey had the highest rates in 2019. The year 2019 also saw the highest death rate among those aged 70 and over, with over 91000 DALYs from IE. DALYs decreased by 71.5% for children under five from 1990 to 2019 but remained stable for individuals in their seventies. Jordan showed the most notable decrease in ASRs for deaths, DALYs, and YLLs among children under five. CONCLUSION: This study highlights the changing epidemiology of IE in the NAME region, recommending the establishment of multidisciplinary IE registries, antibiotic prophylaxis guidelines for healthcare-associated IE, and strategies to control antimicrobial resistance as key mitigation measures.

COVID-19 and MAFLD/NAFLD: An updated review.

The COVID-19 pandemic is ongoing and places a substantial burden on healthcare systems worldwide. As we further shed light on different disease characteristics, we identify more and more groups of people at higher risk of poor COVID-19 outcomes. Metabolic-associated fatty liver disease (MAFLD) (previously non-alcoholic fatty liver disease or NAFLD) is a common metabolic disorder characterized by fat accumulation and liver fibrosis. Given its close correlation with metabolic syndrome, an established risk factor for severe COVID-19, it is necessary to investigate its interplay with the novel coronavirus. In this study, we review the available data on COVID-19 prognosis, treatment and prevention options in patients with MAFLD, and the effect that the disease and the pandemic have on MAFLD care. Furthermore, we point out the gaps in the current literature to accentuate the work that needs to be done to improve MAFLD care during the pandemic and beyond.

Immune checkpoint inhibitors in advanced cutaneous melanoma: a systematic review and meta-analysis of efficacy and review of characteristics.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of all studied ICIs. METHODS: We conducted a comprehensive search to identify the relevant publications (PROSPERO registration ID: CRD42023470649). Then we performed a meta-analysis to evaluate the efficacy of different ICIs for metastatic melanoma. We used Cochrane's tool to assess the quality of studies. The outcome measures were overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). RESULTS: Twenty reports of RCTs entered our systematic review, 18 of which were included in our data analysis. ICIs showed improved survival compared with control group (hazard ratio (HR) = 0.57; 95% CI: 0.43-0.71; P<0.001). Using a meta-regression, we found a significant relation between patients' mean age and their OS (P<0.001, R2 = 100.00%). Also, our analysis revealed greater HR for CTLA-4 inhibitors than PD-1/PD-L1 inhibitors (HR = 0.71, 95%CI: 0.63-0.79, P<0.001 vs. HR = 0.63, 95%CI: 0.46-0.79, P<0.001). The effect sizes of different types of PD-1/PD-L1 inhibitors were comparable. CONCLUSION: Our results suggest that ICI-based immunotherapy is associated with enhanced OS, PFS, and RFS (P < 0.001) and will assist clinicians in choosing the optimal approach toward treating metastatic melanoma.

Direct Mechanical Thrombectomy Versus Prior Bridging Intravenous Thrombolysis in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The current guideline recommends using an intravenous tissue-type plasminogen activator (IV tPA) prior to mechanical thrombectomy (MT) in eligible acute ischemic stroke (AIS) with emergent large vessel occlusion (ELVO). Some recent studies found no significant differences in the long-term functional outcomes between bridging therapy (BT, i.e., IV tPA prior to MT) and direct MT (dMT). METHODS: We conducted a systematic review and meta-analysis to compare the safety and functional outcomes between BT and dMT in AIS patients with ELVO who were eligible for IV tPA administration. Based on the ELVO location, patients were categorized as the anterior group (occlusion of the anterior circulation), or the combined group (occlusion of the anterior and/or posterior circulation). A subgroup analysis was performed based on the study type, i.e., RCT and non-RCT. RESULTS: Thirteen studies (3985 patients) matched the eligibility criteria. Comparing the BT and dMT groups, no significant differences in terms of mortality and good functional outcome were observed at 90 days. Symptomatic intracranial hemorrhagic (sICH) events were more frequent in BT patients in the combined group (OR = 0.73, p = 0.02); this result remained significant only in the non-RCT subgroup (OR = 0.67, p = 0.03). The RCT subgroup had a significantly higher rate of successful revascularization in BT patients (OR = 0.73, p = 0.02). CONCLUSIONS: Our meta-analysis uncovered no significant differences in functional outcome and mortality rate at 90 days between dMT and BT in patients with AIS who had ELVO. Although BT performed better in terms of successful recanalization rate, there is a risk of increased sICH rate in this group.

Effect of famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection: A randomized, double-blind, and placebo-controlled study.

OBJECTIVES: This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial. METHODS: A total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded. RESULTS: At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects. CONCLUSION: Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19. TRIAL REGISTRATION: This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).

COVID-19-induced silent myocarditis and newly developed hypertension in a 3-year-old boy.

BACKGROUND: COVID-19 myocarditis occurs in 7-28% of patients admitted in the hospital with or without multisystem inflammatory syndrome. It may present as fulminant myocarditis. Dilated cardiomyopathy as a sequela of COVID-19 myocarditis has been reported in the pediatric population. However, to date, no case of silent COVID-19 myocarditis progressing to dilated cardiomyopathy has been reported in children. Furthermore, although newly developed hypertension as a sequela of COVID-19 infection has been reported in adults, there is no report of newly developed COVID-induced hypertension in children. We report a 3-year-old boy with silent COVID-19 myocarditis progressing to dilated cardiomyopathy and newly developed systemic hypertension. CASE PRESENTATION: A 3-year-old boy was referred to the emergency department because of respiratory distress. The parents gave a history of SARS-CoV-2 infection in the child 5 months ago that was manifested as fever and cough, for which he was treated as an outpatient. Echocardiographic examination revealed a severe decrease in left ventricular systolic function in favor of dilated cardiomyopathy. Cardiac magnetic resonance imaging established the diagnosis of myocarditis. The patient left ventricular systolic function did not improve after 2 weeks of intravenous inotropic support. Therefore, the child was transferred to another tertiary center with extracorporeal membrane oxygenation and pediatric cardiac transplantation facilities. CONCLUSIONS: COVID-19 can induce silent myocarditis with progression to dilated cardiomyopathy and newly developed systemic hypertension. Thus, a thorough examination of the heart and measurement of blood pressure are mandatory in every child with COVID-19 infection. Cardiac MR is an indispensable tool in the diagnosis, follow-up, and prognostication of COVID-19 myocarditis. Moreover, four-chamber speckle tracking strain imaging showed apical rocking in all the four heart chambers in this child with opposite direction in the failed left ventricle compared with other cardiac chambers. Lastly, the presence of septal flash on M-mode echocardiography, apical rocking and prestretch-rebound stretch patterns on longitudinal strain imaging of the failed left ventricle in this child may be of predictive value for response to cardiac resynchronization therapy.

Artificial Intelligence in Rheumatoid Arthritis: Current Status and Future Perspectives: A State-of-the-Art Review.

Investigation of the potential applications of artificial intelligence (AI), including machine learning (ML) and deep learning (DL) techniques, is an exponentially growing field in medicine and healthcare. These methods can be critical in providing high-quality care to patients with chronic rheumatological diseases lacking an optimal treatment, like rheumatoid arthritis (RA), which is the second most prevalent autoimmune disease. Herein, following reviewing the basic concepts of AI, we summarize the advances in its applications in RA clinical practice and research. We provide directions for future investigations in this field after reviewing the current knowledge gaps and technical and ethical challenges in applying AI. Automated models have been largely used to improve RA diagnosis since the early 2000s, and they have used a wide variety of techniques, e.g., support vector machine, random forest, and artificial neural networks. AI algorithms can facilitate screening and identification of susceptible groups, diagnosis using omics, imaging, clinical, and sensor data, patient detection within electronic health record (EHR), i.e., phenotyping, treatment response assessment, monitoring disease course, determining prognosis, novel drug discovery, and enhancing basic science research. They can also aid in risk assessment for incidence of comorbidities, e.g., cardiovascular diseases, in patients with RA. However, the proposed models may vary significantly in their performance and reliability. Despite the promising results achieved by AI models in enhancing early diagnosis and management of patients with RA, they are not fully ready to be incorporated into clinical practice. Future investigations are required to ensure development of reliable and generalizable algorithms while they carefully look for any potential source of bias or misconduct. We showed that a growing body of evidence supports the potential role of AI in revolutionizing screening, diagnosis, and management of patients with RA. However, multiple obstacles hinder clinical applications of AI models. Incorporating the machine and/or deep learning algorithms into real-world settings would be a key step in the progress of AI in medicine.

Immune modulations and immunotherapies for Alzheimer's disease: a comprehensive review.

Alzheimer's disease (AD), the most common cause of dementia, is characterized by progressive cognitive and memory impairment ensued from neuronal dysfunction and eventual death. Intraneuronal deposition of tau proteins and extracellular senile amyloid-ß plaques have ruled as the supreme postulations of AD for a relatively long time, and accordingly, a wide range of therapeutics, especially immunotherapies have been implemented. However, none of them resulted in significant positive cognitive outcomes. Especially, the repetitive failure of anti-amyloid therapies proves the inefficiency of the amyloid cascade hypothesis, suggesting that it is time to reconsider this hypothesis. Thus, for the time being, the focus is being shifted to neuroinflammation as a third core pathology in AD. Neuroinflammation was previously considered a result of the two aforementioned phenomena, but new studies suggest that it might play a causal role in the pathogenesis of AD. Neuroinflammation can act as a double-edged sword in the pathogenesis of AD, and the activation of glial cells is indispensable for mediating such attenuating or detrimental effects. The association of immune-related genes polymorphisms with the clinical phenotype of AD as well as the protective effect of anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs supports the possible causal role of neuroinflammation in AD. Here, we comprehensively review immune-based therapeutic approaches toward AD, including monoclonal antibodies and vaccines. We also discuss their efficacy and underlying reasons for shortcomings. Lastly, we highlight the capacity of modulating the neuroimmune interactions and targeting neuroinflammation as a promising opportunity for finding optimal treatments for AD.

Microstructural white matter alterations associated with migraine headaches: a systematic review of diffusion tensor imaging studies.

The pathophysiology of migraine as a headache disorder is still undetermined. Diffusion tensor imaging (DTI) has significantly improved our knowledge about brain microstructure in this disease. Here, we aimed to systematically review DTI studies in migraine and survey the sources of heterogeneity by investigating diffusion parameter changes associated with clinical characteristics and migraine subtypes. Microstructural changes, as revealed by widespread alteration of diffusion metrics in white matter (WM) tracts, subcortical and cortical regions, were reported by several migraine DTI studies. Specifically, we reported changes in the corpus callosum, thalamic radiations, corona radiata, and brain stem. These alterations showed high variability across migraine cycle phases. Additionally, migraine associated with depressive/anxiety symptoms revealed significant changes in the corpus callosum, internal capsule, and superior longitudinal fasciculus. No significant WM microstructural differences were observed between migraine patients with and without aura. Overall, differences between chronic and episodic migraine showed inconsistency across studies. Migraine is associated with microstructural changes in widespread regions including thalamic radiations, corpus callosum, and brain stem. These alterations can highlight neuronal damage and neuronal plasticity mechanisms either following pain stimulations occurring in migraine cycle or as a compensatory response to pain in chronic migraine. Longitudinal studies applying advanced modalities may shed new light on the underlying microstructural changes in migraine subtypes.

Imaging of intestinal vasculitis focusing on MR and CT enterography: a two-way street between radiologic findings and clinical data.

Diagnosis of intestinal vasculitis is often challenging due to the non-specific clinical and imaging findings. Vasculitides with gastrointestinal (GI) manifestations are rare, but their diagnosis holds immense significance as late or missed recognition can result in high mortality rates. Given the resemblance of radiologic findings with some other entities, GI vasculitis is often overlooked on small bowel studies done using computed tomography/magnetic resonance enterography (CTE/MRE). Hereon, we reviewed radiologic findings of vasculitis with gastrointestinal involvement on CTE and MRE. The variety of findings on MRE/CTE depend upon the size of the involved vessels. Signs of intestinal ischemia, e.g., mural thickening, submucosal edema, mural hyperenhancement, and restricted diffusion on diffusion-weighted imaging, are common in intestinal vasculitis. Involvement of the abdominal aorta and the major visceral arteries is presented as concentric mural thickening, transmural calcification, luminal stenosis, occlusion, aneurysmal changes, and collateral vessels. Such findings can be observed particularly in large- and medium-vessel vasculitis. The presence of extra-intestinal findings, including within the liver, kidneys, or spleen in the form of focal areas of infarction or heterogeneous enhancement due to microvascular involvement, can be another radiologic clue in diagnosis of vasculitis. The link between the clinical/laboratory findings and MRE/CTE abnormalities needs to be corresponded when it comes to the diagnosis of intestinal vasculitis.

Epidemiology, burden, and attributable risks of infective endocarditis in Iran and its provinces: From 1990 to 2019.

BACKGROUND: Endocarditis is a potentially life-threatening infectious disease associated with significant morbidity and mortality and an escalating incidence in recent decades. In this study, as a part of the global burden of disease (GBD) 2019 study, we intend to report endocarditis burden in Iran at national and provincial levels from 1990 to 2019. METHOD: This study was conducted using GBD 2019 study data on endocarditis from 1990 to 2019. We gathered incidence, prevalence, disability-adjusted life years (DALYs), and mortality rates in Iran and its 31 provinces by sex and age groups as epidemiological indices for endocarditis burden. Further decomposition analysis was also performed to delineate the endocarditis new cases trend. RESULTS: On the country scale, age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate were (16.5 (95% uncertainty interval 13.7 to 19.8), 3.4 (2.9 to 4.1), 0.6 (0.5 to 0.9), and 14.4 (12.0 to 21.1) in 2019, respectively. Decomposition analysis showed that only 59.2% of the overall new cases increase (114.1%) was caused by the incidence rate change. All estimated age-standardized rates were higher in men in 1990 and 2019 with a ratio of 1.1-1.5. CONCLUSION: The ASIR and ASPR of endocarditis increased, and the ASMR and age-standardized DALYs rate declined over the past 30 years in Iran, nearly all the provinces followed the same pattern with North Khorasan having the Highest ASIR, ASPR, ASMR, and DALYs rates in both years. High systolic blood pressure (SBP) had the greatest attributed burden among risk factors.

Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials.

BACKGROUND: Exercise training may affect the blood levels of brain-derived neurotrophic factor (BDNF), but meta-analyses have not yet been performed comparing pre- and post-intervention BDNF concentrations in patients with multiple sclerosis (PwMS). OBJECTIVE: To perform a meta-analysis to study the influence of exercise on BDNF levels and define components that modulate them across clinical trials of exercise training in adults living with multiple sclerosis (MS). METHOD: Five databases (PubMed, EMBASE, Cochrane Library, PEDro database, CINAHL) were searched up to June 2021. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 13 articles in the meta-analysis, including 271 subjects. To investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. We performed the meta-analysis to compare pre- and post-exercise peripheral levels of BDNF in PwMS. RESULTS: Post-exercise concentrations of serum BDNF were significantly higher than pre-intervention levels (Standardized Mean Difference (SMD): 0.33, 95% CI: [0.04; 0.61], p-value = 0.02). Meta-regression indicated that the quality of the included studies based on the PEDro assessment tool might be a source of heterogeneity, while no significant effect was found for chronological age and disease severity according to the expanded disability status scale. CONCLUSION: This systematic review and meta-analysis shows that physical activity increases peripheral levels of BDNF in PwMS. More research on the effect of different modes of exercise on BDNF levels in PwMS is warranted.

Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients.

BACKGROUND: Dedicator of Cytokinesis 8 (DOCK8) deficiency, the most frequent cause of autosomal recessive hyper immunoglobulin (Ig)E syndrome, is a rare combined immunodeficiency. OBJECTIVE: In this study, we report seven patients, with consanguineous parents, with five novel variants within the DOCK8 gene. METHODS: For genetic analysis, we performed Whole Exome Sequencing (WES) or targeted sequencing by means of Next-generation sequencing (NGS) for some of the patients. For others, Sanger sequencing, Fluorescence-activated cell sorting (FACS), or polymerase chain reaction (PCR) were used. RESULTS: We report five novel variants within the DOCK8 gene: three deletions (deletion of exons 4-12, 24-30, and 22-27), one frameshift (LRG_196:g.189315dup;p.(Leu1052Profs*7)), and a splice region variant (LRG_196t1:c.741+5G>T). Patients presented with skin lesions, food allergy, candidiasis, otitis, recurrent respiratory infections, short stature, aortic aneurism, gynecomastia, and coarse facial features. Patients had leukocytosis, eosinophilia, lymphopenia, and monocytosis, elevated IgE, IgG, IgA, reduced IgM and IgA levels. Patients had a low percentage of CD3+ and CD4+ cells and a high percentage of CD19+, CD27+CD19+, and recent thymic emigrants T cells. The percentage of natural killer cells was increased in one of the patients while it was decreased in another patient. One patient died due to disseminated intravascular coagulation after hematopoietic stem cell transplantation. CONCLUSION: We reported novel variants within the DOCK8 gene and highlighted the risk of aneurysms in these patients, which have been rarely reported in these patients.