Diagnostic and Therapeutic Challenges of Rare Concurrent Intracranial Meningioma and Oligodendroglioma.

Introduction: Concurrent primary brain tumors are rare clinical entities, with a prevalence ranging from 0.1 to 0.5% of all diagnosed brain tumors. The co-occurrence of meningioma and oligodendroglioma is particularly uncommon, posing unique diagnostic and therapeutic challenges. We describe the case of a patient diagnosed with concurrent meningioma and oligodendroglioma and review the existing literature on this rare phenomenon. Case Presentation: A 55-year-old female patient with a history of seizures presented to the emergency department with worsening headaches, nausea, and vomiting. She had a known right frontoparietal intracranial mass but had previously declined surgery. Magnetic resonance imaging revealed extensive fluid-attenuated inversion recovery /T2 hyperintensity around the lesion, which had slowly increased over 5 years; the growth of the lesion was producing a mass effect with a significant midline shift. The patient underwent urgent hemicraniectomy with subsequent resection. Clinical evaluation, imaging studies, and histopathological examination were conducted to confirm the diagnosis. Genetic and molecular analyses were also performed to explore potential underlying mechanisms. Histopathological findings confirmed a diagnosis of an isocitrate dehydrogenase-mutated World Health Organization Grade II oligodendroglioma with 1p/19q codeletion, along with a Grade I meningioma. Conclusion: The coexistence of meningioma and oligodendroglioma represents a rare clinical event. Surgical management remains the cornerstone of treatment. Further investigation into the genetic and environmental factors that contribute to the co-occurrence of such tumors could pave the way for more targeted therapeutic strategies.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

Prediction Model for Neurogenic Bladder Recovery One Year After Traumatic Spinal Cord Injury.

INTRODUCTION: Neurogenic bladder is a common complication after spinal cord injury (SCI) that carries substantial burdens on the inflicted individual. The objective of this study is to build a prediction model for neurogenic bladder recovery 1 year after traumatic SCI. METHODS: We queried the National Spinal Cord Injury Model Systems database for patients with traumatic SCI who had neurogenic bladder at the time of injury. The primary outcome of interest was the complete recovery of bladder function at 1 year. Multiple imputations were performed to generate replacement values for missing data, and the final imputed data were used for our analysis. A multivariable odds logistic regression model was developed for complete bladder recovery at 1 year. RESULTS: We identified a total of 2515 patients with abnormal bladder function at baseline who had an annual follow-up. A total of 417 patients (16.6%) recovered bladder function in 1 year. Predictors of complete bladder recovery included the following baseline parameters: sacral sensation, American Spinal Injury Association (ASIA) impairment score, bowel function at baseline, voluntary sphincter contraction, anal sensation, S1 motor scores, and the number of days in the rehabilitation facility. The model performed with a discriminative capacity of 90.5%. CONCLUSIONS: We developed a prediction model for the probability of complete bladder recovery 1 year after SCI. The model performed with a high discriminative capacity. This prediction model demonstrates potential utility in the counseling, research allocation, and management of individuals with SCI.

Bone morphogenetic proteins in spine surgery: a scientometric analysis to date.

OBJECTIVE: Bone morphogenetic proteins (BMPs) are part of the transforming growth factor-beta superfamily and are involved in bone formation and repair. In spine surgery, recombinant human BMP (rhBMP) is used as an alternative to autografts for spinal fusions. This study aimed to evaluate bibliometric parameters and citations of the literature on BMPs to provide an overview of how the field has evolved. METHODS: A comprehensive search of the literature was conducted using Elsevier's Scopus database to capture all the published and indexed studies relevant to BMPs from 1955 to the present. A discrete set of validated bibliometric parameters was extracted and analyzed. All statistical analyses were performed using R 4.1.1. RESULTS: The 100 most cited articles were published between 1994 and 2018 by 472 unique authors in 40 sources (e.g., journals and books). On average, there were 279 citations per publication and 17.69 citations per publication per year. The United States had the publications with the most citations (n = 23,761), followed by Hong Kong (n = 580) and the United Kingdom (n = 490). The three institutions in the United States with the greatest number of publications in the field were Emory University (n = 14), Hughston Clinic (n = 9), Hospital for Special Surgery (n = 6), and University of California (n = 6). CONCLUSIONS: The authors evaluated and characterized the 100 most cited articles about BMP. Most of the publications were clinical in nature and focused on BMP's application in spine surgery. While early scientific efforts focused on basic science research to advance the understanding of BMP's mechanism of action in promoting bone formation, the majority of the more recent publications are clinically focused. It will be beneficial to conduct more controlled clinical trials to compare the outcomes of BMP use with other methods.

Central neurocytomas: research trends, most cited papers, and scientometrics analysis to date.

Central neurocytoma is the most common primary intraventricular tumor in adults being classified by the World Health Organization (WHO) as a benign grade II tumor with a good prognosis. Given the recent advances with regard to this tumor, a bibliometric analysis was due to study the future direction of research for neurocytomas. A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies to date relevant to neurocytoma. A discrete set of validated bibliometric parameters were extracted and analyzed on R v4.1.3. A total of 1002 documents were included in our analysis covering a period between 1910 and 2021 (111 years). Around 98.5% of the documents were multi-author publications with a collaboration index (CI) of 4.21. Acta Neuropathologica, The American Journal of Surgical Pathology, and Cancer were the journals to include the highest number of top ten cited articles (2 out of 10 most cited articles, 20%). Switzerland (4 out of 10, 40%) accounted for the country to have the highest number of top 10 most cited articles with the USA (5588 out of 16,395 citations, 34.1%) having the greatest number of citations. Lastly, our analysis reported an annual growth rate of 6.9% for the number of papers produced by year. This is the first bibliometric analysis to study the top 10 most cited articles with regard to neurocytomas. A shift from histopathologic and clinical symptoms towards the treatment and management of the tumor was observed in our analysis.

Mapping the Landscape of Neurofibromatosis: A Bibliometric Evaluation Highlighting Our Current Understanding, Emerging Therapies, and Global Research Trends.

BACKGROUND: The literature on neurofibromatosis (NF) has never been systematically assessed using bibliometric analytic methodologies. We quantitatively analyzed the major trends and scientific output regarding NF, highlighting potential avenues for research. METHODS: An Elsevier's Scopus database search was performed for all indexed studies related to NF from 1898 to 2021. Validated bibliometric parameters were analyzed using productivity, citation, and keyword analysis, including text mining, content analysis, and collaboration network mapping from inception to date on R 4.1.2. RESULTS: Our search yielded 15,024 documents. Annual scientific production has grown at a compounded rate of 5.86%, with the largest occurring in 2021 (n = 626). Journals with the most publications on NF include the Journal of Medical Genetics (n = 117) and Neurology (n = 113). The topmost cited author was Gutmann DH (n = 295). The United States had the most international collaboration (n = 435; multiple country publications). Identification of citation classics revealed a shift in recent decades towards understanding genetic and molecular pathways of NF tumorigenesis. Macro-level and micro-level text mining revealed the top 20 genetic and molecular pathways, and syndromes, associated with NF. CONCLUSIONS: Our study exemplifies a quantitative method for understanding the historical and current state of academic efforts regarding NF. There has been a shift of treatment strategies towards targeting specific pathways involved in tumorigenesis. We highlight the top 20 genetic and molecular pathways in the literature as well as the top 20 associated syndromes. This data is encouraging as increased research in molecular targeted therapies aimed at NF pathogenesis may allow advances in disease control.

The Impact of Major Military War Campaigns on Neurosurgery: Informetric Data and Time-Trend Analysis.

BACKGROUND: Given the neurotrauma that soldiers might face during wars, a byproduct of such devastating neurosurgical conditions can be novel data, which can act as a catalyst for potentially paradigm-shifting research. We aimed to identify the impact of major U.S. military campaigns on military neurosurgery literature across defined time periods. METHODS: A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies from 1915 to 2021 relevant to military neurosurgery. A discrete set of validated informetric metadata parameters were extracted and analyzed using productivity analysis, citation analysis, keyword analysis, text mining, content analysis, and collaboration network mapping. RESULTS: Our search yielded 2216 documents. Annual scientific production since 1915 grew at a compounded rate of 6.1% per year, with the most significant increases during U.S. military campaigns (coefficient = 42.9, P < 0.001) and following the introduction of the Department of Defense Trauma Registry in 2007 (coefficient = 114.5; P < 0.001). Each war had a direct influence on military neurosurgery literature growth (P < 0.05), with the most prominent following the Afghanistan war. The journals with the most publications on military neurosurgery were Military Medicine (n = 168) and Journal of Head Trauma. The topmost cited author was Hoge et al. (N = 2083), while the topmost cited country was the United States (N = 1098). CONCLUSIONS: Since World War II, the military has contributed significant historical developments to neurosurgery, the most prominent being after the Iraq and Afghanistan wars and the introduction of the Department of Defense Trauma Registry.

Impact of ACE2 genetic variant on antidepressant efficacy of SSRIs.

Identification of a new axis of angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7)/Mas receptor, in the renin-angiotensin system (RAS), has opened a new insight regarding the role of RAS and angiotensin in higher brain functions. ACE2 catabolizes angiotensin II and produces angiotensin (1-7), an agonist of Mas receptor. Mice lacking the Mas receptor (angiotensin 1-7 receptor) exhibit anxiety-like behaviours. The present study was conducted to test the hypothesis of the involvement of ACE2 genetic variant (G8790A) on response to selective serotonin reuptake inhibitors (SSRIs). In a randomised control trial, 200 newly diagnosed Iranian patients with major depressive disorder completed 6 weeks of fluoxetine or sertraline treatment. Patients with a reduction of 50% or more in the Hamilton Rating Scale for Depression score were considered responsive to treatment. G8790A polymorphism was determined in extracted DNAs using restriction fragment length polymerase chain reaction method. Our results show that the A allele and AA and GA genotypes were significantly associated with better response to SSRIs (p = 0.008; OR = 3.4; 95% CI = 1.4-8.5 and p = 0.027; OR = 3.3, 95% CI = 1.2-9.2, respectively). Moreover, patients with GA and AA genotypes responded significantly better to sertraline (p = 0.0002; OR = 9.1; 95% CI = 2.4-33.7). The A allele was significantly associated with better response to sertraline (p = 0.0001; OR = 7.6; 95% CI = 2.5-23.3). In conclusion, our results confirm the role of G8790A in response to some SSRIs.

Glucose-Regulated Protein 78 Autoantibodies Are Associated with Carotid Atherosclerosis in Chronic Obstructive Pulmonary Disease Patients.

Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors. The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response. Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease. We hypothesized anti-GRP78 autoreactivity might also be a risk factor for atherosclerosis in COPD patients. Carotid intima-medial thickness (cIMT) was measured in 144 current and former smokers by ultrasound. Concentrations of circulating IgG autoantibodies against full-length GRP78, determined by ELISA, were greater among subjects with abnormally increased cIMT (p < 0.01). Plasma levels of autoantibodies against a singular GRP78 peptide segment, amino acids 246-260 (anti-GRP78aa 246-260), were even more highly correlated with cIMT, especially among males with greater than or equal to moderate COPD (r s = 0.62, p = 0.001). Anti-GRP78aa 246-260 concentrations were independent of CRP, IL-6, and TNF-α levels. GRP78 autoantigen expression was upregulated among human aortic endothelial cells (HAECs) stressed by incubation with tunicamycin (an unfolded protein response inducer) or exposure to culture media flow disturbances. Autoantibodies against GRP78aa 246-260, isolated from patient plasma by immunoprecipitation, induced HAEC production of proatherosclerotic mediators, including IL-8. In conclusion, anti-GRP78 autoantibodies are highly associated with carotid atherosclerosis in COPD patients and exert atherogenic effects on HAECs. These data implicate Ag-specific autoimmunity in the pathogenesis of atherosclerosis among COPD patients and raise possibilities that directed autoantibody reduction might ameliorate vascular disease in this high-risk population.

Influence of ACE gene on differential response to sertraline versus fluoxetine in patients with major depression: a randomized controlled trial.

BACKGROUND: Extensive distribution of the different components of renin angiotensin system (RAS) in the brain, along with their roles in promoting anxiety, depression and brain inflammation, opposes RAS as a potential therapeutic target in major depression. Actions of angiotensin II, the main product of RAS, are reduced by antidepressants and this signifies the complex interplay of different mechanisms involved in response to therapy. Here, we hypothesized that genetic polymorphisms of RAS may affect the outcome of therapy in depressed patients. METHODS: The frequencies of variants of genes encoding for angiotensin-converting enzyme (ACE) insertion/deletion (I/D), rs4291 and rs4343 polymorphisms were determined in extracted DNAs of 200 newly diagnosed depressed patients. Patients were randomly divided into two groups, one treated with fluoxetine and the other treated with sertraline for 12 weeks. Responsive patients were determined by psychiatrist using Hamilton questionnaire and were compared with regard to their genetic variants. RESULTS: Carriers of the D allele and patients with DD genotype responded significantly better to sertraline than to fluoxetine (P = 0.0006, odds ratio (OR) = 3.0, 95 % confidence interval (CI) = 1.80-5.08; P = 0.006, OR = 3.7, 95 % CI = 1.66-8.29, respectively). Mutant genotypes (GG and TT) of rs4343 and rs4291 polymorphisms were also more frequent in patients responding to sertraline, though not achieving the significance level (P = 0.162 and P = 0.256, respectively). CONCLUSION: These findings suggest that special genetic variants of RAS may influence or be an indicator for better response to sertraline.

Robot body self-modeling algorithm: a collision-free motion planning approach for humanoids.

Motion planning for humanoid robots is one of the critical issues due to the high redundancy and theoretical and technical considerations e.g. stability, motion feasibility and collision avoidance. The strategies which central nervous system employs to plan, signal and control the human movements are a source of inspiration to deal with the mentioned problems. Self-modeling is a concept inspired by body self-awareness in human. In this research it is integrated in an optimal motion planning framework in order to detect and avoid collision of the manipulated object with the humanoid body during performing a dynamic task. Twelve parametric functions are designed as self-models to determine the boundary of humanoid's body. Later, the boundaries which mathematically defined by the self-models are employed to calculate the safe region for box to avoid the collision with the robot. Four different objective functions are employed in motion simulation to validate the robustness of algorithm under different dynamics. The results also confirm the collision avoidance, reality and stability of the predicted motion.

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study.

BACKGROUND: Autism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism. METHODS: Considering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: There were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64-5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37-3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26-2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008). CONCLUSION: Our data suggests the involvement of RAS genetic diversity in increasing the risk of autism.

Airflow Limitation and Endothelial Dysfunction. Unrelated and Independent Predictors of Atherosclerosis.

RATIONALE: Lower FEV1 is associated with increased prevalence of atherosclerosis; however, causal mechanisms remain elusive. OBJECTIVES: To determine if systemic endothelial dysfunction mediates the association between reduced FEV1 and increased atherosclerosis. METHODS: Brachial artery endothelial function, pulmonary function, coronary artery calcium, and carotid plaque were assessed in 231 Pittsburgh SCCOR (Specialized Centers for Clinically Oriented Research) study participants; peripheral arterial endothelial function, pulmonary function, and coronary artery calcium were assessed in 328 HeartSCORE (Heart Strategies Concentrating on Risk Evaluation) study participants. MEASUREMENTS AND MAIN RESULTS: Lower FEV1 was independently associated with increased atherosclerosis in both cohorts (per 25% lower % predicted FEV1: odds ratio [OR], 1.76; 95% confidence interval [CI], 1.30-2.40; P < 0.001 for carotid plaque in SCCOR participants) (per 25% lower % predicted FEV1: OR, 1.35; 95% CI, 1.02-1.77; P = 0.03 for coronary artery calcium in HeartSCORE participants). Similarly, reduced endothelial function was independently associated with increased atherosclerosis in both cohorts (per SD lower endothelial function: OR, 1.30; 95% CI, 1.01-1.67; P = 0.04 for carotid plaque in SCCOR participants) (per SD lower endothelial function: OR, 1.38; 95% CI, 1.09-1.76; P = 0.008 and OR, 1.41; 95% CI, 1.07-1.86; P = 0.01 for coronary artery calcium in SCCOR and HeartSCORE participants, respectively). However, there was no association between endothelial dysfunction and FEV1, FEV1/FVC, low-attenuation area/visual emphysema, and diffusing capacity in SCCOR participants, and between endothelial dysfunction and FEV1 or FEV1/FVC in HeartSCORE participants (all P > 0.05). Adjusting the association between FEV1 and atherosclerosis for endothelial dysfunction had no impact. CONCLUSIONS: Endothelial dysfunction does not mediate the association between airflow limitation and atherosclerosis. Instead, airflow limitation and endothelial dysfunction seem to be unrelated and mutually independent predictors of atherosclerosis.

Cardiac CD47 drives left ventricular heart failure through Ca2+-CaMKII-regulated induction of HDAC3.

BACKGROUND: Left ventricular heart failure (LVHF) remains progressive and fatal and is a formidable health problem because ever-larger numbers of people are diagnosed with this disease. Therapeutics, while relieving symptoms and extending life in some cases, cannot resolve this process and transplant remains the option of last resort for many. Our team has described a widely expressed cell surface receptor (CD47) that is activated by its high-affinity secreted ligand, thrombospondin 1 (TSP1), in acute injury and chronic disease; however, a role for activated CD47 in LVHF has not previously been proposed. METHODS AND RESULTS: In experimental LVHF TSP1-CD47 signaling is increased concurrent with up-regulation of cardiac histone deacetylase 3 (HDAC3). Mice mutated to lack CD47 displayed protection from transverse aortic constriction (TAC)-driven LVHF with enhanced cardiac function, decreased cellular hypertrophy and fibrosis, decreased maladaptive autophagy, and decreased expression of HDAC3. In cell culture, treatment of cardiac myocyte CD47 with a TSP1-derived peptide, which binds and activates CD47, increased HDAC3 expression and myocyte hypertrophy in a Ca(2+)/calmodulin protein kinase II (CaMKII)-dependent manner. Conversely, antibody blocking of CD47 activation, or pharmacologic inhibition of CaMKII, suppressed HDAC3 expression, decreased myocyte hypertrophy, and mitigated established LVHF. Downstream gene suppression of HDAC3 mimicked the protective effects of CD47 blockade and decreased hypertrophy in myocytes and mitigated LVHF in animals. CONCLUSIONS: These data identify a proximate role for the TSP1-CD47 axis in promoting LVHF by CaKMII-mediated up-regulation of HDAC3 and suggest novel therapeutic opportunities.

Executive Functions among Traumatic Injury Patients: Comparison of Normal Individuals and those with Attention Deficit Hyperactivity Disorder.

OBJECTIVES: To describe the executive function of patients with traumatic injury admitted to Rajaei hospital, Shiraz, Iran and to compare the executive function between normal individuals and those with Attention Deficit Hyperactivity Disorder (ADHD). METHODS: This was a case control study being performed during a 6-month period during spring and summer of 2013 in Shiraz level I trauma center. We included all patients admitted during the study period with impression of traumatic injury with or without adult ADHD. The patients' demographic factors were assessed through self-report questionnaire and executive functions by Wisconsin Card Sort Test (WCST) and Tower of London (TOL). Results were compared between normal individuals and those with ADHD. RESULTS: Among 60 patients evaluated during the study period, with impression of traumatic injury, 29 fulfilled adult ADHD criteria and 31 were normal. The mean age of ADHD patients was 27.16±5.6 years and that of normal individuals was 26±3.4 years (p=0.330). There were no significant differences between two study groups regarding IQ (p=0.191) and education (p=0.396). Patients with ADHD had significantly poorer mean in executive functions in different parts of the test scoring system when compared to normal individuals. CONCLUSION: ADHD patients  with  traumatic  injury  had  poor  executive function  compared  to  normal individuals. This might lead to poor inhibition, shifting and problem solving in this population.

Fulminant hepatitis following chemotherapy treatment for breast cancer.

A woman in her early 50s was admitted to the intensive care unit with nausea, altered mental status and hepatic failure. She had a history of asymptomatic chronic hepatitis B and recently received chemotherapy for breast cancer. A diagnosis of hepatitis B reactivation (HBR) was made, but unfortunately she died of liver failure. Controversies around testing for hepatitis B prior to giving immunosuppressive treatments and the use of prophylactic antiviral therapy to prevent HBR are discussed.

Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach.

Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized. An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched. From one hundred twenty five retrieved titles, 12 (three case control study and 9 case reports) articles met inclusion criteria. All of the included studies indicated dysfunction of electron transport chain in autism. The mitochondrial electron transfer chain seems impaired in some children with autism and ROS production is additionally enhanced. It is hypothesized that interventions involving alternative electron shuttling may improve autism through lowering the production of ROS. In addition, it is expected that this alternative electron shuttling to cytochrome c might enhance the production of ATP which is impaired in the disorder.