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Schizophrenia Bulletin Jun 2024N-Methyl-d-aspartate receptor (NMDA-R) hypofunctioning has been hypothesized to be involved in circuit dysfunctions in schizophrenia (ScZ). Yet, it remains to be...
Effects of N-Methyl-d-Aspartate Receptor Antagonists on Gamma-Band Activity During Auditory Stimulation Compared With Electro/Magneto-encephalographic Data in Schizophrenia and Early-Stage Psychosis: A Systematic Review and Perspective.
BACKGROUND AND HYPOTHESIS
N-Methyl-d-aspartate receptor (NMDA-R) hypofunctioning has been hypothesized to be involved in circuit dysfunctions in schizophrenia (ScZ). Yet, it remains to be determined whether the physiological changes observed following NMDA-R antagonist administration are consistent with auditory gamma-band activity in ScZ which is dependent on NMDA-R activity.
STUDY DESIGN
This systematic review investigated the effects of NMDA-R antagonists on auditory gamma-band activity in preclinical (n = 15) and human (n = 3) studies and compared these data to electro/magneto-encephalographic measurements in ScZ patients (n = 37) and 9 studies in early-stage psychosis. The following gamma-band parameters were examined: (1) evoked spectral power, (2) intertrial phase coherence (ITPC), (3) induced spectral power, and (4) baseline power.
STUDY RESULTS
Animal and human pharmacological data reported a reduction, especially for evoked gamma-band power and ITPC, as well as an increase and biphasic effects of gamma-band activity following NMDA-R antagonist administration. In addition, NMDA-R antagonists increased baseline gamma-band activity in preclinical studies. Reductions in ITPC and evoked gamma-band power were broadly compatible with findings observed in ScZ and early-stage psychosis patients where the majority of studies observed decreased gamma-band spectral power and ITPC. In regard to baseline gamma-band power, there were inconsistent findings. Finally, a publication bias was observed in studies investigating auditory gamma-band activity in ScZ patients.
CONCLUSIONS
Our systematic review indicates that NMDA-R antagonists may partially recreate reductions in gamma-band spectral power and ITPC during auditory stimulation in ScZ. These findings are discussed in the context of current theories involving alteration in E/I balance and the role of NMDA hypofunction in the pathophysiology of ScZ.
PubMed: 38934800
DOI: 10.1093/schbul/sbae090 -
Journal of Diabetes and Metabolic... Jun 2024Efpeglenatide, a novel GLP-1 receptor agonist, has shown promise in improving glycemic control and inducing weight loss in individuals with type 2 diabetes (T2DM). This... (Review)
Review
BACKGROUND
Efpeglenatide, a novel GLP-1 receptor agonist, has shown promise in improving glycemic control and inducing weight loss in individuals with type 2 diabetes (T2DM). This meta-analysis assessed its therapeutic potential and safety profile.
METHODS
A literature search was conducted on PubMed, SCOPUS, and Cochrane Central from inception until September 2023. We selected patients with T2DM and identified and compared those receiving efpeglenatide to placebo. Outcomes assessed included fasting plasma glucose (FPG), HbA1c, body weight, BMI, and cardiometabolic parameters. Data were analyzed using a random-effects model, with results presented as mean differences (MD) for continuous outcomes and risk ratios (RR) for safety analysis, along with their respective 95% confidence intervals. Quality assessment was conducted using the Cochrane risk of bias tool.
RESULTS
We included 11 studies in our analysis. Efpeglenatide demonstrated significant reductions in FPG (MD = -1.53 mmol/L, 95% CI = [-2.86, -0.66], < 0.01), HbA1c (MD = -0.84, 95% CI= [-1.08, -0.60], < 0.01), body weight (MD = -2.24 kg, 95% CI = [-4.20, -2.00], < 0.01), and BMI (MD = -1.61 kg/m, 95% CI= [-2.12, -1.09], < 0.01). However, efpeglenatide was associated with a moderate increase in the risk of gastrointestinal adverse events, nausea, diarrhea, and vomiting. There was a non-significant elevated risk of hypoglycemia.
CONCLUSIONS
Efpeglenatide significantly improves glycemic outcomes and promotes weight loss in individuals with diabetes. However, it is associated with moderate adverse effects related to the gastrointestinal system. Thus, further trials are warranted to comprehensively assess its safety and efficacy to derive a robust conclusion.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01409-3.
PubMed: 38932865
DOI: 10.1007/s40200-024-01409-3 -
Neuropsychopharmacology Reports Jun 2024Bipolar disorder (BD) has a significant impact on global health, yet its neurophysiological basis remains poorly understood. Conventional treatments have limitations,... (Review)
Review
AIM
Bipolar disorder (BD) has a significant impact on global health, yet its neurophysiological basis remains poorly understood. Conventional treatments have limitations, highlighting the need for a better understanding of the neurophysiology of BD for early diagnosis and novel therapeutic strategies.
DESIGN
Employing a systematic review approach of the PRISMA guidelines, this study assessed the usefulness and validity of transcranial magnetic stimulation (TMS) neurophysiology in patients with BD.
METHODS
Databases searched included PubMed, MEDLINE, Embase, and PsycINFO, covering studies from January 1985 to January 2024.
RESULTS
Out of 6597 articles screened, nine studies met the inclusion criteria, providing neurophysiological insights into the pathophysiological basis of BD using TMS-electromyography and TMS-electroencephalography methods. Findings revealed significant neurophysiological impairments in patients with BD compared to healthy controls, specifically in cortical inhibition and excitability. In particular, short-interval cortical inhibition (SICI) was consistently diminished in BD across the studies, which suggests a fundamental impairment of cortical inhibitory function in BD. This systematic review corroborates the potential utility of TMS neurophysiology in elucidating the pathophysiological basis of BD. Specifically, the reduced cortical inhibition in the SICI paradigm observed in patients with BD suggests gamma-aminobutyric acid (GABA)-A receptor-mediated dysfunction, but results from other TMS paradigms have been inconsistent. Thus, complex neurophysiological processes may be involved in the pathological basis underlying BD. This study demonstrated that BD has a neural basis involving impaired GABAergic function, and it is highly expected that further research on TMS neurophysiology will further elucidate the pathophysiological basis of BD.
PubMed: 38932486
DOI: 10.1002/npr2.12458 -
International Journal of Molecular... Jun 2024A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory... (Review)
Review
A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of "Neuroinflammation", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: "High mobility group box 1/HMGB1", "Toll-Like-Receptor 4/TLR-4", "Interleukin-1/IL-1", "Interleukin-6/IL-6", "Transforming growth factor beta/TGF-β", and "Tumour necrosis factor-alpha/TNF-α". These queries were all combined with the MESH terms "Epileptogenesis" and "Epilepsy". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.
Topics: Humans; Biomarkers; Neuroinflammatory Diseases; HMGB1 Protein; Epilepsy; Cytokines; Toll-Like Receptor 4; Drug Resistant Epilepsy
PubMed: 38928193
DOI: 10.3390/ijms25126488 -
Biomedicines May 2024Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is... (Review)
Review
Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance.
PubMed: 38927416
DOI: 10.3390/biomedicines12061209 -
Neurological Research and Practice Jun 2024This review specifically investigates ketamine's role in SRSE management. (Review)
Review
OBJECTIVE
This review specifically investigates ketamine's role in SRSE management.
METHODS
PubMed, EMBASE, and Google Scholar databases were searched from inception to May 1st, 2023, for English-language literature. Inclusion criteria encompassed studies on SRSE in humans of all ages and genders treated with ketamine.
RESULTS
In this systematic review encompassing 19 studies with 336 participants, age ranged from 9 months to 86 years. Infections, anoxia, and metabolic issues emerged as the common causes of SRSE, while some cases had unknown origins, termed as NORSE (New Onset RSE) or FIRESs (Febrile Infection-Related Epilepsy Syndrome). Most studies categorized SRSE cases into convulsive (N = 105) and non-convulsive (N = 197). Ketamine was used after failed antiepileptics and anesthetics in 17 studies, while in others, it was a first or second line of treatment. Dosages varied from 0.5 mg/kg (bolus) and 0.2-15 mg/kg/hour (maintenance) in adults and 1-3 mg/kg (bolus) and 0.5-3 mg/kg/hour (maintenance) in pediatrics, lasting one to 30 days. Ketamine was concurrently used with other drugs in 40-100% of cases, most frequently propofol and midazolam. Seizure resolution rate varied from 53.3 to 91% and 40-100% in larger (N = 42-68) and smaller case series (N = 5-20) respectively. Seizure resolution occurred in every case of case report except in one in which the patient died. Burst suppression in EEG was reported in 12 patients from two case series and two case reports. Recurrence was reported in 11 patients from five studies. The reported all-cause mortality varied from 38.8 to 59.5% and 0-36.4% in larger and smaller case series., unrelated directly to ketamine dosage or duration.
SIGNIFICANCE
Ketamine demonstrates safety and effectiveness in SRSE, offering advantages over GABAergic drugs by acting on NMDA receptors, providing neuroprotection, and reducing vasopressor requirement.
PubMed: 38926769
DOI: 10.1186/s42466-024-00322-7 -
Epilepsy & Behavior : E&B Jun 2024Pathogenesis of epilepsy involves dysregulation of the neurotransmitter system contributing to hyper-excitability of neuronal cells. MicroRNA (miRNAs) are small... (Review)
Review
BACKGROUND
Pathogenesis of epilepsy involves dysregulation of the neurotransmitter system contributing to hyper-excitability of neuronal cells. MicroRNA (miRNAs) are small non-coding RNAs known to play a crucial role in post-transcriptional regulation of gene expression.
METHODS
The present review was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, employing a comprehensive search strategy to identify and extract data from published research articles. Keywords suchas epilepsy, micro RNA (micro RNAs, miRNA, miRNAs, miR), neurotransmitters (specific names), and neurotransmitter receptors (specific names) were used to construct the query.
RESULTS
A total of 724 articles were identified using the keywords epilepsy, microRNA along with select neurotransmitter and neurotransmitter receptor names. After exclusions, the final selection consisted of 17 studies, most of which centered on glutamate and gamma-aminobutyric acid (GABA) receptors. Singular studies also investigated miRNAs affecting cholinergic, purinergic, and glycine receptors.
CONCLUSION
This review offers a concise overview of the current knowledge on miRNA-mediated regulation of neurotransmitter receptors in epilepsy and highlights their potential for future clinical application.
PubMed: 38924965
DOI: 10.1016/j.yebeh.2024.109912 -
Journal of Clinical Neuroscience :... Jun 2024Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of... (Review)
Review
BACKGROUND
Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of clazosentan, an endothelin receptor antagonist, in reducing CV, delayed cerebral ischemia (DCI), and the need for rescue therapy in aSAH patients, while evaluating its impact on functional outcomes and mortality.
METHODS
We conducted a literature search across multiple databases to identify relevant studies evaluating the effects of clazosentan in aSAH patients. Both cohort studies and randomized controlled trials (RCTs) were included. The primary outcomes were vasospasm incidence, moderate to severe vasospasm, DCI, and the need for rescue therapy. Secondary outcomes included functional outcomes, mortality, and adverse events. The data were pooled as Risk ratios (R/R) with 95 % confidence intervals (CI) using RevMan 5.4 software.
RESULTS
A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta-analysis. Clazosentan significantly reduced the incidence of vasospasm (R/R = 0.49: 0.34-0.70), moderate to severe vasospasm (R/R = 0.53: 0.46-0.61), DCI (R/R = 0.70: 0.59-0.82), and the need for rescue therapy (R/R = 0.65: 0.52-0.83) compared to placebo. However, no significant improvement in functional outcomes or mortality rates was observed. Clazosentan was associated with increased rates of pulmonary adverse events (R/R = 1.89: 1.64-2.18), hypotension (R/R = 2.47: 1.79-3.42), and anemia (R/R = 1.49: 1.23-1.79) but no increased risk of hepatobiliary adverse events or cerebral hemorrhage.
CONCLUSIONS
Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm.
PubMed: 38924824
DOI: 10.1016/j.jocn.2024.06.019 -
Tomography (Ann Arbor, Mich.) Jun 2024CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's... (Review)
Review
CAR-T-cell therapy, also referred to as chimeric antigen receptor T-cell therapy, is a novel method in the field of immunotherapy for the treatment of non-Hodgkin's lymphoma (NHL). In patients receiving CAR-T-cell therapy, fluorodeoxyglucose Positron Emission Tomography/Computer Tomography ([F]FDG PET/CT) plays a critical role in tracking treatment response and evaluating the immunotherapy's overall efficacy. The aim of this study is to provide a systematic review of the literature on the studies aiming to assess and predict toxicity by means of [F]FDG PET/CT in patients with NHL receiving CAR-T-cell therapy. PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were interrogated by two investigators to seek studies involving the use of [F]FDG PET/CT in patients with lymphoma undergoing CAR-T-cell therapy. The comprehensive computer literature search allowed 11 studies to be included. The risk of bias for the studies included in the systematic review was scored as low by using version 2 of the "Quality Assessment of Diagnostic Accuracy Studies" tool (QUADAS-2). The current literature emphasizes the role of [F]FDG PET/CT in assessing and predicting toxicity in patients with NHL receiving CAR-T-cell therapy, highlighting the evolving nature of research in CAR-T-cell therapy. Additional studies are warranted to increase the collected evidence in the literature.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Lymphoma, Non-Hodgkin; Immunotherapy, Adoptive; Radiopharmaceuticals; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 38921943
DOI: 10.3390/tomography10060066 -
Current Issues in Molecular Biology May 2024Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age, representing the primary cause of anovulatory infertility.... (Review)
Review
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age, representing the primary cause of anovulatory infertility. The nonapeptide oxytocin (OT) plays an important role in cognitive, emotional, and reproductive functions in human beings. Oxytocin receptors are expressed in several body parts, including the ovaries. Despite this, the possible role played by oxytocin in symptoms of PCOS is not clear. The present systematic review aimed at understanding the presence of possible oxytocin level alterations in PCOS, the connection between alterations of OT levels and the symptoms of PCOS, and the effect of oxytocin administration in PCOS. After a systematic search in the principal databases, eight studies, five human and three animal, were included. Four human studies and one animal study highlighted the role played by oxytocin in fertility issues related to PCOS. Three human and two animal studies investigated the role of body weight and OT levels. Studies that analyzed oxytocin basal levels in women agreed that PCOS is associated with a reduction in the serum level of oxytocin. Two human studies and one animal study agreed about lower levels of oxytocin, confirming a possible implication of the dysfunction of OT in the pathogenesis of PCOS.
PubMed: 38920985
DOI: 10.3390/cimb46060313