Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study.

BACKGROUND: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. METHODS: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. CONCLUSIONS: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

Clinging on the brink: Whole genomes reveal human-induced population declines and severe inbreeding in the Critically Endangered Emirati Leaf-toed Gecko (Asaccus caudivolvulus).

Human-mediated habitat destruction has had a profound impact on increased species extinction rates and population declines worldwide. The coastal development in the United Arab Emirates (UAE) over the last two decades, serves as an example of how habitat transformation can alter the landscape of a country in just a few years. Here, we study the genomic implications of habitat transformation in the Critically Endangered Emirati Leaf-toed Gecko (Asaccus caudivolvulus), the only endemic vertebrate of the UAE. We generate a high-quality reference genome for this gecko, representing the first reference genome for the family Phyllodactylidae, and produce whole-genome resequencing data for 23 specimens from 10 different species of leaf-toed geckos. Our results show that A. caudivolvulus has consistently lower genetic diversity than any other Arabian species of Asaccus, suggesting a history of ancient population declines. However, high levels of recent inbreeding are recorded among populations in heavily developed areas, with a more than 50% increase in long runs of homozygosity within a 9-year period. Moreover, results suggest that this species does not effectively purge deleterious mutations, hence making it more vulnerable to future stochastic threats. Overall, results show that A. caudivolvulus is in urgent need of protection, and habitat preservation must be warranted to ensure the species' survival.

Mild hypophosphatasia may be twice as prevalent as previously estimated: an effective clinical algorithm to detect undiagnosed cases.

OBJECTIVES: Since the prevalence of hypophosphatasia (HPP), a rare genetic disease, seems to be underestimated in clinical practice, in this study, a new diagnostic algorithm to identify missed cases of HPP was developed and implemented. METHODS: Analytical determinations recorded in the Clinical Analysis Unit of the Hospital Universitario Clínico San Cecilio in the period June 2018 - December 2020 were reviewed. A new clinical algorithm to detect HPP-misdiagnosed cases was used including the following steps: confirmation of persistent hypophosphatasemia, exclusion of secondary causes of hypophosphatasemia, determination of serum pyridoxal-5'-phosphate (PLP) and genetic study of ALPL gene. RESULTS: Twenty-four subjects were selected to participate in the study and genetic testing was carried out in 20 of them following clinical algorithm criteria. Eighty percent of patients was misdiagnosed with HPP following the current standard clinical practice. Extrapolating these results to the current Spanish population means that there could be up to 27,177 cases of undiagnosed HPP in Spain. In addition, we found a substantial proportion of HPP patients affected by other comorbidities, such as autoimmune diseases (∼40 %). CONCLUSIONS: This new algorithm was effective in detecting previously undiagnosed cases of HPP, which appears to be twice as prevalent as previously estimated for the European population. In the near future, our algorithm could be globally applied routinely in clinical practice to minimize the underdiagnosis of HPP. Additionally, some relevant findings, such as the high prevalence of autoimmune diseases in HPP-affected patients, should be investigated to better characterize this disorder.

Retinal shadows produced by myopia control spectacles.

PURPOSE: To analyse ocular coherence tomography (OCT) images of the retinal shadows caused by defocus and diffusion optics spectacles. METHODS: One eye was fitted successively with the Hoya Defocus Incorporated Multiple Segments (DIMS) spectacle lens, two variations of the +3.50 D peripheral add spectacle (DEFOCUS) and the low-contrast dot lens (Diffusion Optics Multiple Segments, DOMS); each at a vertex distance of 12 mm. Simultaneously, a retinal image of the macular region with central fixation was obtained using infrared OCT. The corneal power and intraocular distances were determined using an optical biometer. RESULTS: The retinal images for the DIMS and DOMS lenses showed patterns of obvious retinal shadows in the periphery, while the central 10-11° remained clear. The DEFOCUS lens produced a darkened peripheral area. Dividing the size of the retinal pattern, measured with the calliper of the OCT software, by the actual size on the spectacle lens gave a magnification of -0.57 times. This is consistent with the incoming OCT beam being imaged to a position approximately 31 mm beyond the front of the eye. [Correction added on 26 October 2023 after first online publication: The preceding paragraph was corrected.] CONCLUSION: With device-specific correction, retinal OCT images can help visualise the regions affected by the defocus or lowered contrast induced by myopia control spectacles. This is of potential value for improving myopia therapies.

Survival and neurological outcomes following management of intramedullary spinal metastasis patients: a case series with comprehensive review of the literature.

Intramedullary spinal cord metastasis (ISCM), though rare, represents a potentially debilitating manifestation of systemic cancer. With emerging advances in cancer care, ISCMs are increasingly being encountered in clinical practice. Herein, we describe one of the larger retrospective single institutional case series on ISCMs, analyze survival and treatment outcomes, and review the literature. All surgically evaluated ISCMs at our institution between 2005 and 2023 were retrospectively reviewed. Demographics, tumor features, treatment, and clinical outcome characteristics were collected. Neurological function was quantified via the Frankel grade and the McCormick score (MCS). The pre- and post-operative Karnofsky performance scores (KPS) were used to assess functional status. Descriptive statistics, univariate analysis, log-rank test, and the Kaplan-Meier survival analysis were performed. A total of 9 patients were included (median age 67 years (range, 26-71); 6 were male). Thoracic and cervical spinal segments were most affected (4 patients each). Six patients (75%) underwent surgical management (1 biopsy and 5 resections), and 3 cases underwent chemoradiation only. Post-operatively, 2 patients had an improvement in their neurological exam with one patient becoming ambulatory after surgery; three patients maintained their neurological exam, and 1 had a decline. There was no statistically significant difference in the pre- and post-operative MCS and median KPS scores in surgically treated patients. Median OS after ISCM diagnosis was 7 months. Absence of brain metastasis, tumor histology (renal and melanoma), cervical/thoracic location, and post-op KPS ≥ 70 showed a trend toward improved overall survival. The incidence of ISCM is increasing, and earlier diagnosis and treatment are considered key for the preservation of neurological function. When patient characteristics are favorable, surgical resection of ISCM can be considered in patients with rapidly progressive neurological deficits. Surgical treatment was not associated with an improvement in overall survival in patients with ISCMs.

Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose.

Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood-brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function.

Dental color measurement to estimate age in adults: a systematic review and meta-analysis.

Age estimation is a major challenge in anthropology and forensic odontology laboratories, as well as in judicial settings, as one of the tools used in human identification. The aim of this study was to evaluate the usefulness of age estimation methods based on the accurate measurement of tooth color changes. A systematic review was carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and in compliance with Cochrane criteria recommendations (PROSPERO registration number CRD 42022343371). An electronic search was performed in the following databases: Pubmed, Web of Science, Medline, Current Contents Connect, SciELO, KCI-Korean Journal Database, Derwent Innovations Index and Russian Citation Index. The search strategy yielded a total of 18 articles. A randomized meta-analysis model of the results for the CIE L*a*b* color variables stratified by age (less than 30 years, 30-60 years, 60 years and older) was performed with 9 of the 18 studies included in this systematic review. According to our results, sex and location of color measurement are the most influential factors in color estimation. All studies were carried out in healthy anterior teeth by spectrophotometry as the most commonly used method for color measurement, with CIE L*a*b* being the most commonly analyzed parameters. Studies based on age as a dependent variable showed R2 values between 0.28 and 0.56, being higher in ex vivo teeth. Studies based on age as an independent variable showed R2 values ranging from 0.10 to 0.48. The random model showed high heterogeneity for the L*, a* and b* parameters in all age groups, which is explained by discrepancies in age range and non-standardized conditions for color measurement. This systematic review highlights the need to protocolize age estimation studies that measure tooth color, in order to apply this method in different forensic settings.

Comparing Functional Outcomes and Safety Profiles of First-Line Aspiration Thrombectomy Versus Stentriever for Acute Basilar Artery Occlusion: Propensity Analysis of the PC-SEARCH Thrombectomy Registry.

BACKGROUND: Aspiration catheters (ASPs) and stentriever thrombectomy devices have comparable safety and efficacy in anterior circulation ischemic strokes. However, there is lack of high-quality comparative data in acute basilar artery occlusions. Our objective is to compare the outcomes and safety of ASPs and stentriever devices in acute basilar artery occlusions. METHODS: This is an analysis of the retrospectively established PC-SEARCH Thrombectomy (Posterior-Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy) registry. Patients were dichotomized based on their first-line thrombectomy device (ASP and stentriever) and associated with their 90-day functional outcomes, intraprocedural metrics, and safety measures. Propensity analysis based on unequal baseline characteristics was performed. Consecutive patients with acute basilar artery occlusions who received mechanical thrombectomy were included from January 2015 to December 2021. Patients received either first-line contact aspiration or stentriever mechanical thrombectomy. Primary clinical and safety outcomes were 90-day functional independence measured by a modified Rankin Scale score of 0 to 3 and symptomatic intracranial hemorrhage, respectively. Secondary outcomes included puncture-recanalization times, first-pass recanalization rates, crossovers to other thrombectomy device, and neurological/hospital complications. RESULTS: Five hundred eighteen patients were included in the registry, and a total of 383 patients were included (mean [SD] age, 65.5 [15] years; 228 [59%] men) in this analysis. Of these, 219 patients were first-line ASP while 164 patients received first-line stentriever devices. Median premorbid modified Rankin Scale was zero and median presenting National Institutes of Health Stroke Scale was 17 (interquartile range, 8-26). The proportion of favorable functional outcome was similar between the 2 techniques before (47.3% versus 42.5%; odds ratio, 1.22 [95% CI, 0.78-1.89]; P=0.38) and after propensity matching (odds ratio, 1.46 [95% CI, 0.85-2.49]; P=0.17). In our propensity-matched cohorts, puncture-recanalization times (18 versus 52 minutes; P<0.01) favored first-line ASP; however, first-pass recanalization rates (43.5% versus 44.5%; P=0.90) were similar between groups. First-line ASP was associated with higher rates of crossover (22% versus 6%; P<0.01), whereas stentriever was associated with higher rates of symptomatic intracranial hemorrhage (9.8% versus 3.4%; P=0.04). CONCLUSIONS: First-line ASP and stentriever methods demonstrated similar functional outcome and recanalization rates. Stentriever methods were associated with higher rates of symptomatic intracranial hemorrhage, whereas ASPs were associated with higher rates of crossover to alternative technique in patients with acute basilar occlusions.

Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions.

BACKGROUND: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment. METHODS: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality. RESULTS: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P=0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P=0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P=0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P=0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P=0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups. CONCLUSIONS: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days.

Transcending the amyloid-beta dominance paradigm in Alzheimer's disease: An exploration of behavioural, metabolic, and gut microbiota phenotypes in 5xFAD mice.

The amyloid cascade hypothesis is widely accepted as an explanation for the neuropathological changes in Alzheimer's disease (AD). However, the role of amyloid-beta (Aß) as the sole cause of these changes is being questioned. Using the 5xFAD mouse model of AD, we investigated various factors contributing to neuropathology, including genetic load (heterozygous (HTZ) versus homozygous (HZ) condition), behavioural phenotype, neuropathology markers, metabolic physiology, and gut microbiota composition at early (5 months of age) and late (12 months of age) stages of disease onset, and considering both sexes. At 5 months of age, both HTZ and HZ mice exhibited hippocampal alterations associated with Aß accumulation, leading to increased neuroinflammation and disrupted PI3K-Akt pathway. However, only HZ mice showed cognitive impairment in the Y-maze and Morris water maze tests, worsening with age. Dysregulation of both insulin and insulin secretion-regulating GIP peptide were observed at 5 months of age, disappearing later. Circulating levels of metabolic-regulating hormones, such as Ghrelin and resisting helped to differentiates HTZ mice from HZ mice. Differences between HTZ and HZ mice were also observed in gut microbiota composition, disrupted intestinal barrier proteins, and increased proinflammatory products in the intestine. These findings suggest that cognitive impairment in 5xFAD mice may not solely result from Aß aggregation. Other factors, including altered PI3K-Akt signalling, disrupted insulin-linked metabolic pathways, and changes in gut microbiota, contribute to disease progression. Targeting Aß deposition alone may not suffice. Understanding AD pathogenesis and its multiple contributing factors is vital for effective therapies.

Generalist arbuscular mycorrhizal fungi dominated heavy metal polluted soils at two artisanal and small - scale gold mining sites in southeastern Ecuador.

BACKGROUND: Artisanal and small-scale gold mining activities are producing contamination with heavy metals and metalloids (HMM) into soils and water worldwide. The HMM are considered as one of the major abiotic stresses due to their long-term persistence in soil. In this context, arbuscular mycorrhizal fungi (AMF) confer resistance to a variety of abiotic plant stressors including HMM. However, little is known regarding the diversity and composition of AMF communities in heavy metal polluted sites in Ecuador. METHODS: In order to investigate the AMF diversity, root samples and associated soil of six plant species were collected from two sites polluted by heavy metals, located in Zamora-Chinchipe province, Ecuador. The AMF 18S nrDNA genetic region was analyzed and sequenced, and fungal OTUs were defined based on 99% sequence similarity. Results were contrasted with AMF communities from a natural forest and from reforestation sites located in the same province and with available sequences in GenBank. RESULTS: The main pollutants in soils were Pb, Zn, Hg, Cd and Cu with concentrations exceeding the soil reference value for agricultural use. Molecular phylogeny and OTU delimitation showed 19 OTUs, the family Glomeraceae was the most OTU-rich followed by Archaeosporaceae, Acaulosporaceae, Ambisporaceae and Paraglomeraceae. Most of the OTUs (11 of 19) have been found at other locations worldwide, 14 OTUs were proven from nearby non-contaminated sites in Zamora-Chinchipe. CONCLUSION: Our study showed that there are no specialized OTUs at the studied HMM polluted sites, but rather generalists adapted to a wide variety of habitats. Their potential role in phytoremediation approaches remains to be investigated.

Postoperative de novo epilepsy after resection of brain arteriovenous malformations: A national database study of 536 patients.

OBJECTIVE: We aimed to assess the incidence and risk factors for de novo epilepsy after arteriovenous malformation (AVM) resection and compare them with a nonresection cohort after propensity score matching, utilizing a national database. METHODS: Utilizing the TriNetX Research Network, we queried cases from January 1, 2004 to March 1, 2022. We included patients of all ages who underwent supratentorial AVM resection, presenting without seizures on or before surgery and without being on antiseizure medications at least 1 day before surgery. The primary outcome was seizures manifesting at least 6 weeks after surgery. Patient characteristics and outcomes were compared between the cohorts with and without postoperative epilepsy. Further cohorts were created to compare cohorts with and without embolization or rupture. After propensity score matching, we compared an additional cohort of patients with an AVM diagnosis who did not undergo resection. RESULTS: Of the 536 patients (mean age = 38.9 ± 19.6, 52% females) presenting without seizure who underwent AVM resection, 99 (18.5%) developed de novo epilepsy, with a 1-year cumulative incidence of 13.8%. Patients with epilepsy had higher rates of intracerebral hemorrhage, and intracerebral hemorrhage was less common in the embolization cohort. Patients in the ruptured cohort were older and more often males. After propensity score matching with 18 588 patients with AVM diagnosis but no resection, each group consisted of 529 patients, and de novo epilepsy at 1 year was significantly higher in the AVM resection cohort compared to the nonresection cohort (11.5% vs. 3.4%, p < .001). SIGNIFICANCE: This analysis of 536 patients provides evidence that de novo epilepsy after brain AVM resection occurs at a 1-year cumulative incidence of 13.8%, with a total of 19.4% developing de novo epilepsy. Intracerebral hemorrhage was inconsistently associated with postoperative de novo epilepsy. De novo epilepsy was significantly less frequent after AVM diagnosis without resection.

Risk factors associated with acute kidney injury in a cohort of hospitalized patients with COVID-19.

BACKGROUND: Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19. METHODOLOGY: A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission. RESULTS: A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73-2.99), age (OR 1.02, 95% CI 1.01-1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03-6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10-20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14-1.71), the use of vancomycin (OR 1.57, 95% CI 1.05-2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2-2.31), and vasopressor support (CI 2.39, 95% CI 1.53-3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI. CONCLUSIONS: This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19.

Surgical management of craniospinal axis malignant peripheral nerve sheath tumors: a single-institution experience and literature review.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an exceedingly rare and aggressive tumor, with limited literature on its management. Herein, we present our series of surgically managed craniospinal MPNSTs, analyze their outcomes, and review the literature. METHODS: We retrospectively reviewed surgically managed primary craniospinal MPNSTs treated at our institution between January 2005 and May 2023. Patient demographics, tumor features, and treatment outcomes were assessed. Neurological function was quantified using the Frankel grade and Karnofsky performance scores. Descriptive statistics, rank-sum tests, and Kaplan-Meier survival analyses were performed. RESULTS: Eight patients satisfied the inclusion criteria (4 male, 4 female). The median age at presentation was 38 years (range 15-67). Most tumors were localized to the spine (75%), and 3 patients had neurofibromatosis type 1. The most common presenting symptoms were paresthesia (50%) and visual changes (13%). The median tumor size was 3 cm, and most tumors were oval-shaped (50%) with well-defined borders (75%). Six tumors were high grade (75%), and gross total resection was achieved in 5 patients, with subtotal resection in the remaining 3 patients. Postoperative radiotherapy and chemotherapy were performed in 6 (75%) and 4 (50%) cases, respectively. Local recurrence occurred in 5 (63%) cases, and distant metastases occurred in 2 (25%). The median overall survival was 26.7 months. Five (63%) patients died due to recurrence. CONCLUSIONS: Primary craniospinal MPNSTs are rare and have an aggressive clinical course. Early diagnosis and treatment are essential for managing these tumors. In this single-center study with a small cohort, maximal resection, low-grade pathology, young age (< 30), and adjuvant radiotherapy were associated with improved survival.

Safety and efficacy of the p48 MW and p64 flow modulation devices: a systematic review and meta-analysis.

OBJECTIVE: Flow diverters (FDs) have demonstrated increasing safety and efficacy in treating various types of intracranial aneurysms. Although the underlying mechanism of action of all FDs is similar, differences are noted in their intrinsic characteristics, materials, and deployment techniques. The p64 flow modulation device (p64) and the newer p48 movable wire flow modulation device (p48 MW) are not yet available in the US but have been increasingly used mainly in Europe, demonstrating optimistic results. The authors performed a systematic review and meta-analysis of the literature to evaluate the safety and efficacy of the p64 and p48 MW FDs. METHODS: A literature review (between January 1960 and November 2022) of the PubMed, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases was conducted. The primary efficacy outcome was the proportion of complete angiographic occlusion at last follow-up. Complete occlusion was defined as Raymond-Roy class 1 and O'Kelly-Marotta grade D. The primary safety outcomes were the composite safety rate of ischemic and hemorrhagic events (intra- and postprocedure) and the all-cause mortality rate. Data were analyzed using a random-effects proportions meta-analysis, and statistical heterogeneity was assessed. RESULTS: Twenty studies with 1781 patients harboring 1957 aneurysms were included in the analysis. Seventeen studies were conducted in Europe. Sixteen studies evaluated the performance of the p64 (MW). Patient ages ranged between 20 and 89 years, and most were female (78.7%). Aneurysm size ranged between 1 and 50 mm. Most aneurysms were unruptured (92.8%) and in the anterior circulation (93.1%). Single antiplatelet therapy pre- and postprocedure was used in 2 studies. Follow-up ranged from 2 to 14.5 months. For the p64 and p48 MW, complete angiographic occlusion rates were 77% (95% CI 68%-85%) and 67% (95% CI 49%-81%), adjunctive coil usage rates were 7% (95% CI 4%-12%) and 4% (95% CI 0%-24%), primary safety composite rates were 2% (95% CI 1%-4%) and 3% (95% CI 1%-11%), and mortality rates were 0.49% (95% CI 0%-1%) and 2% (95% CI 1%-6%), respectively. CONCLUSIONS: The p64 and p48 MW have primarily been used in Europe thus far. This analysis found that both devices have an acceptable efficacy and favorable safety profile. However, further studies are needed to evaluate the efficacy and safety of prescribing a single antiplatelet regimen after implantation of the newer-generation FDs with antithrombotic coating surface modification.

Partners in Postmortem Interval Estimation: X-ray Diffraction and Fourier Transform Spectroscopy.

The postmortem interval (PMI) is difficult to estimate in later stages of decomposition. There is therefore a need to develop reliable methodologies to estimate late PMI. This study aims to assess whether there is a correlation between changes in the mineral composition of human teeth and the estimation of PMI. X-ray diffraction (XRD) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy techniques were performed to address this challenge. Forty healthy human teeth obtained from odontological clinics were stored at different times (0, 10, 25, 50 years; N = 10/group). XRD and ATR-FTIR parameters related to the structure and composition of teeth were studied. Our results showed that the crystallinity index, crystal size index, mineral-to-organic matrix ratio (M/M) and carbonate/phosphate ratio (C/P) had the strongest association with PMI. For larger PMIs, there was a significant increase in crystallinity, crystal size and M/M ratio, while the C/P ratio showed a specific decrease with increasing PMI. According to our results, the parameters of crystallinity, crystal size, M/M ratio and C/P ratio can be considered highly accurate in determining a PMI of 10 years of data; crystallinity and mineral maturity can be considered useful in determining a PMI of 25 years; and crystallinity and mineral maturity can be considered highly accurate in determining a PMI of 50 years. A particular XRD index was identified as the most suitable parameter to estimate PMI: crystallinity. The joint use of XRD and ATR-FTIR analyses could be a promising alternative for dating human teeth.

Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer's Disease: Implications for Controlling Astroglial Activity.

Alzheimer's disease (AD) is a common neurodegenerative disease. In AD-associated neuroinflammation, astrocytes play a key role, finding glial activation both in patients and in animal models. The endocannabinoid system (ECS) is a neurolipid signaling system with anti-inflammatory and neuroprotective properties implicated in AD. Astrocytes respond to external cannabinoid signals and also have their own cannabinoid signaling. Our main objective is to describe the cannabinoid signaling machinery present in hippocampal astrocytes from 3×Tg-AD mice to determine if they are actively involved in the neurodegenerative process. Primary cultures of astrocytes from the hippocampus of 3×Tg-AD and non-Tg offspring were carried out. We analyzed the gene expression of astrogliosis markers, the main components of the ECS and Ca2+ signaling. 3×Tg-AD hippocampal astrocytes show low inflammatory activity (Il1b, Il6, and Gls) and Ca2+ flow (P2rx5 and Mcu), associated with low cannabinoid signaling (Cnr1 and Cnr2). These results were more evident in females. Our study corroborates glial involvement in AD pathology, in which cannabinoid signaling plays an important role. 3×Tg-AD mice born with hippocampal astrocytes with differential gene expression of the ECS associated with an innate attenuation of their activity. In addition, we show that there are sex differences from birth in this AD animal, which should be considered when investigating the pathogenesis of the disease.

Antipsychotic Medication Influences the Discriminative Value of Acylethanolamides as Biomarkers of Substance Use Disorder.

Plasma acylethanolamides (NAEs), including the endocannabinoid anandamide (AEA), have been proposed as circulating biomarkers of substance use disorders. However, the concentration of these lipid transmitters might be influenced by the use of drugs prescribed for either the treatment of addiction or the associated psychiatric co-morbidities such as psychosis. As an example, neuroleptics, used for attenuation of psychotic symptoms and sedation, might theoretically interfere with the monoamine-mediated production of NAEs, obstructing the interpretation of plasma NAEs as clinical biomarkers. To solve the lack of information on the impact of neuroleptics on the concentration of NAEs, we evaluated the concentrations of NAEs in a control group and compared them to those present in (a) substance use disorders (SUD) patients that are not prescribed with neuroleptics, and (b) SUD patients (both alcohol use disorder and cocaine use disorder patients) using neuroleptics. The results demonstrate that SUD patients exhibited greater concentrations of NAEs than the control population, affecting all species with the exception of stearoylethanolamide (SEA) and palmitoleoylethanolamide (POEA). Neuroleptic treatment enhanced the concentrations of NAEs, especially those of AEA, linoleoylethanolamide (LEA), and oleoylethanolamide (OEA). This effect of neuroleptic treatment was observed independently of the drug addiction that motivated the demand for treatment (either alcohol or cocaine). This study remarks the need to control the current use of psychotropic medication as a potential confounding variable when considering the use of NAEs as biomarkers in SUD.

Antidepressant Medication Does Not Contribute to the Elevated Circulating Concentrations of Acylethanolamides Found in Substance Use Disorder Patients.

Circulating acylethanolamides (NAEs) are bioactive signaling molecules that modulate multiple homeostatic functions including mood and hedonic responses. Variations in their plasma concentrations are associated with substance use disorders (SUD) and recent studies suggest that psychotropic medication might influence its circulating levels, limiting its use as a clinical biomarker of addiction. In addition, they might have a role as mediators of the pharmacological effects of psychotropic drugs. Thus, in mild depression, the response to selective serotonin reuptake inhibitor-type antidepressants (SSRI) is associated with a marked increase in circulating NAEs. To further investigate if antidepressants are able to modify the plasma concentration of NAEs in SUD patients, we analyzed the circulating levels of NAEs in 333 abstinent and 175 healthy controls on the basis of the treatment with SSRI antidepressants. As described previously, SUD patients display higher concentrations of NAEs than those measured in a control population. This increase was not further modified by antidepressant therapy. Only marginal increases in palmitoylethanolamide (PEA), oleoylethanolamide (OEA), or docosatetraenoyl-ethanolamide (DEA) were found, and the net effect was very small. Thus, our study shows that treatment with SSRI-type antidepressants does not modify the clinical utility of monitoring enhanced NAE production as biomarkers of SUD. In addition, the possibility that a blunted NAE response to antidepressant therapy might be related to the loss of efficacy of SSRIs in dual depression emerges as an attractive hypothesis that needs to be addressed in future studies.

Embolization as stand-alone strategy for pediatric low-grade brain arteriovenous malformations.

OBJECTIVES: We evaluated the safety and efficacy of endovascular embolization as first-line stand-alone strategy for the treatment of low-grade brain arteriovenous malformations (bAVMs) (Spetzler Martin [SM] grade I and II) in pediatric patients. In addition, we assessed the predictors of procedure-related complications and radiographic complete obliteration in a single session. MATERIAL AND METHODS: We conducted a single center retrospective cohort study of all pediatric (≤18 years) patients who underwent embolization as a stand-alone strategy for low-grade bAVMs between 2010 and 2022. Safety was measured by procedure-related complications and mortality. Efficacy was defined as complete angiographic obliteration after the last embolization session. RESULTS: Sixty-eight patients (41 females; median age 14 years) underwent a total of 102 embolization sessions. There were 24 (35%) SM grade I lesions and 44 (65%) grade II. Six procedure-related complications (5.8% of procedures) were observed and no deaths were reported. All the complications were intraoperative nidus ruptures. A single draining vein was the only significant predictor of procedure-related complications (OR=0.10; 95% CI 0.01 - 0.72; p=0.048). Complete angiographic obliteration was achieved in 44 patients (65%). In 35 patients (51%) the bAVM was completely occluded in one session. The bAVM nidal size was a predictor of complete obliteration in one session (OR=0.44; 95% CI, 0.21-0.80; p=0.017). CONCLUSION: Endovascular treatment as a stand-alone strategy for pediatric low-grade bAVMs is an adequate first-line approach in high volume centers with endovascular expertise. Nidal size evaluation is relevant in order to optimize patient selection for embolization as a stand-alone treatment modality.