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Introduction: Endolymphatic sac tumor (ELST) is a rare neoplasm that exhibits aggressive growth primarily in the endolymphatic capsule and can potentially affect nearby neurovascular structures. The diagnosis of ELST poses challenges due to its low prevalence, gradual progression, and nonspecific symptomatology. It is currently believed that prompt surgical intervention is recommended for endolymphatic sac tumors upon diagnosis. In cases where the lesion is complex or in close proximity to vital blood vessels and nerves, making complete resection challenging, adjuvant therapy may be employed postoperatively. This approach aims to enhance treatment outcomes. Case presentation: A case of a 53-year-old male was admitted to the Department of Neurosurgery of Shenzhen People's Hospital with the main cause of dizziness and blurred vision, and was found to have an occupation in the pontocerebellar angle for about 20 days. Preoperative cranial CT suggested that the temporal bone mastoid was widely damaged with worm-like bone, and some of them showed honeycomb changes. MRI suggested that shadow was seen in the posterior part of the left internal auditory canal, temporal bone mastoid and jugular foramen, with a size of about 28x21x27mm.The T1-weighted image showed low and equal signals, and the T2-weighted image showed equal and slightly low signals in the center with multicompartmental cystic high signals in the margin. The center of the mass strengthened significantly after enhancement. The patient had no other clinical manifestations and no family history. The clinical diagnosis was left-sided pontocerebellar angle occupation - nature to be determined. The occupation was resected microscopically using the distal lateral combined anterior approach to the sigmoid sinus. Due to the extremely rich blood supply of the tumor, the tumor was embedded in the petrous humerus, which was soft and tough, and the surrounding structures were not clearly displayed, making surgical resection extremely difficult. postoperative pathology and immunohistochemistry confirmed that this lesion was an endolymphatic cystic tumor. After surgery, most of the tumor was successfully resected while preserving neurological function well, and the residual tumor was treated with adjuvant gamma knife with good results. Conclusion: ELST is a rare, low-grade, locally aggressive tumor that is difficult to diagnose early. During the surgery, it was observed that the tumor had a significant blood supply, which made its removal challenging. Preoperative embolization of the tumor's blood supply artery would facilitate surgical resection and help avoid massive intraoperative bleeding. Complete surgical resection is the treatment of choice, and any remaining tumor remnants can be managed with adjuvant radiotherapy post-surgery, necessitating long-term follow-up to monitor any developments. [ABSTRACT FROM AUTHOR]

Introduction: Endolymphatic sac tumors (ELSTs) are rare neuroectodermal neoplasms that originate in the endolymphatic sac and duct. They exhibit no specific age or gender predilection, although they are more prevalent in patients with von Hippel–Lindau syndrome. Material and methods: The manuscript preparation adhered to the CARE guidelines for standardizing clinical cases and the PRISMA guidelines for scientific reviews. Three studies that met the inclusion criteria were selected from an analysis of 15 articles, supplemented by two additional studies identified through citation review. Results: The presented case describes a 16-year-old boy diagnosed with unilateral sensorineural hearing loss secondary to bilateral ELST. Surgical excision of the right ear tumor with simultaneous cochlear implantation was performed, followed by left ear surgery. Hearing restoration was achieved in the implanted right ear, with normal hearing in the left ear, and no postoperative vestibular symptoms were observed. Conclusion: Prompt surgical intervention remains the cornerstone of ELST treatment. While cochlear implantation is sporadically reported in scientific literature, it offers a potential option for hearing improvement in patients suffering from deafness caused by the disease. [ABSTRACT FROM AUTHOR]

Background/Objectives: Intracranial aneurysms (IAs) may be connected to interactions between large and small intracranial vessels. We aimed to investigate the association between IAs and cerebral small-vessel disease (CSVD) and assess CSVD impact on IA patient management. Methods: This retrospective study analyzed clinical data and MRI features of CSVD in 192 subarachnoid hemorrhage (SAH) patients: 136 with incidental IA, 147 with severe CSVD without SAH/IA, and 50 controls without SAH, IA, or severe CSVD. MRI assessments followed the Standards for Reporting Vascular Changes on Neuroimaging (STRIVE), with a total burden of small-vessel disease (TBSVD) score calculated. Statistical analyses included forward selection and binary logistic regression. Results: TBSVD differed significantly across groups (p < 0.001), except between SAH and IA groups (p = 0.8). Controls had the lowest TBSVD (1.00; 1.22 ± 0.996), followed by SAH (2.00; 2.08 ± 1.013) and IA groups (2.00; 2.04 ± 1.141), with the highest in the CSVD group (1.00; 1.22 ± 0.996). White-matter hyperintensity (WMH) patterns varied with IA rupture status (p = 0.044); type A was prevalent in SAH patients and type D in the IA group. Incorporating MRI CSVD features and TBSVD into risk assessments did not enhance IA prediction or outcome models. Conclusions: IA patients exhibit a higher CSVD burden than controls, suggesting a link between small and large intracranial vessels. WMH patterns distinguish between ruptured and unruptured IA patients, offering potential markers for IA rupture risk assessment and signaling a paradigm shift in understanding IAs and CSVD. [ABSTRACT FROM AUTHOR]

This article discusses the "breakwater" technique, a new endovascular treatment method for ruptured intracranial vertebral artery dissecting aneurysms (VADAs) involving the posterior inferior cerebellar artery (PICA). The technique aims to prevent rebleeding and preserve antegrade flow in the PICA. It involves using two microcatheters via the contralateral vertebral artery to perform proximal parent artery occlusion (PAO) and dense coil packing. The article presents a case study and a review of the current literature on endovascular therapy for ruptured VADAs involving the PICA. The technique shows promise but may not be suitable for all patients, and further research is needed to determine its effectiveness and limitations. [Extracted from the article]

Clear-cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild-type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of the mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia (PML) protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 activity and senescence in ccRCC. Treatment with the FDA-approved PML inhibitor arsenic trioxide induced PML degradation and p53 accumulation and inhibited ccRCC expansion in vitro and in vivo. Therefore, by defining non-oncogene addiction to the PML gene, our work uncovers a novel ccRCC vulnerability and lays the foundation for repurposing an available pharmacological intervention to restore p53 function and chemosensitivity. Synopsis: The promyelocytic leukemia protein (PML) is essential to sustain clear cell renal cell carcinoma (ccRCC) expansion via p53 inhibition and the PML-targeting drug arsenic trioxide exerts cancer inhibitory functions in ccRCC. PML is overexpressed and efficiently partitioned into PML-NBs in ccRCC. PML inhibition blocks ccRCC expansion in vitro and in vivo. Targeting ccRCC non-oncogenic addiction to PML via gene silencing or arsenic trioxide unleashes p53-dependent growth arrest and apoptosis. Arsenic trioxide is effective at inhibiting expansion of ccRCC cells with wild type and mutant p53. The promyelocytic leukemia protein (PML) is essential to sustain clear cell renal cell carcinoma (ccRCC) expansion via p53 inhibition and the PML-targeting drug arsenic trioxide exerts cancer inhibitory functions in ccRCC. [ABSTRACT FROM AUTHOR]

We highlight the particular aspects of the stable gastric pentadecapeptide BPC 157 pleiotropic beneficial activity (not destroyed in human gastric juice, native and stable in human gastric juice, as a cytoprotection mediator holds a response specifically related to preventing or recovering damage as such) and its possible relations with neurotransmitter activity. We attempt to resolve the shortage of the pleiotropic beneficial effects of BPC 157, given the general standard neurotransmitter criteria, in classic terms. We substitute the lack of direct conclusive evidence (i.e., production within the neuron or present in it as a precursor molecule, released eliciting a response on the receptor on the target cells on neurons and being removed from the site of action once its signaling role is complete). This can be a network of interconnected evidence, previously envisaged in the implementation of the cytoprotection effects, consistent beneficial particular evidence that BPC 157 therapy counteracts dopamine, serotonin, glutamate, GABA, adrenalin/noradrenalin, acetylcholine, and NO-system disturbances. This specifically includes counteraction of those disturbances related to their receptors, both blockade and over-activity, destruction, depletion, tolerance, sensitization, and channel disturbances counteraction. Likewise, BPC 157 activates particular receptors (i.e., VGEF and growth hormone). Furthermore, close BPC 157/NO-system relations with the gasotransmitters crossing the cell membrane and acting directly on molecules inside the cell may envisage particular interactions with receptors on the plasma membrane of their target cells. Finally, there is nerve-muscle relation in various muscle disturbance counteractions, and nerve-nerve relation in various encephalopathies counteraction, which is also exemplified specifically by the BPC 157 therapy application. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. Method: A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients' airways was evaluated preoperatively and postoperatively in intensive-care units. Results: POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. Conclusions: The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: While noninvasive imaging is typically used during the initial assessment of carotid artery disease, digital subtraction angiography remains the gold standard for evaluating carotid stent thrombosis and stenosis (Krawisz in Cardiol Clin 39:539–549, 2021). This case highlights the importance of digital subtraction angiography for assessing carotid artery stent patency in place of non-invasive imaging. Case presentation: We present a 61-year-old African American male patient with a history of right cervical internal carotid artery dissection that was treated with carotid artery stenting and endovascular thrombectomy, who developed recurrent right hemispheric infarcts related to delayed carotid stent thrombosis. Digital subtraction angiography found multiple filling defects consistent with extensive in-stent thrombosis not clearly observed with magnetic resonance angiography. Etiology was likely secondary to chronic antiplatelet noncompliance. Therefore, the patient was treated medically with a heparin drip, and dual antiplatelet therapy (dAPT) was restarted. At 1-month follow-up the patient did not report new motor or sensory deficits. Conclusion: In the setting of delayed carotid stent thrombosis secondary to antiplatelet noncompliance, digital subtraction angiography may play an essential diagnostic role for early identification and determination of the most appropriate treatment. [ABSTRACT FROM AUTHOR]

To explore the potential role of microRNA miR-221-5p on the angiopoietin-1 (Ang-1)/Ang-2/Tie-2 signaling axis after subarachnoid hemorrhage (SAH) in a rat model. Aspects of the rat's behavior were measured using the Kaoutzanis scoring system to test neurological responses. This included feeding behavior, body contraction, motor, and eye-opening responses. Brain sections were studied using transmission electron microscopy and Evans blue extravasation. Levels of Ang-1, Ang-2, and Tie-2 were determined by Western blot, while miR-221-5p was quantified using stem-loop real-time quantitative PCR (RT-qPCR). The SAH group responded worse to the neurological response test than the sham-operated group. The intercellular space was widened in the SAH group, but not in the sham-operated group. Evans blue dye leaked significantly more into brain tissue cells of the SAH group. Stem-loop qRT-PCR showed elevated miR-221-5p levels. Additionally, Ang-1 and Tie-2 were reduced but Ang-2 expression was increased after SAH. This led to a significant reduction of the Ang-1/Ang-2 ratio in the brain tissue, which was associated with the destruction of the blood-brain barrier. The data indicate that miR-221-5p might regulate blood-brain barrier dysfunction through the Ang-1/Ang-2/Tie-2 signaling axis, suggesting that it should be further investigated as a potential novel biomarker. [ABSTRACT FROM AUTHOR]

Background & Purpose: Non-stenotic (< 50%) carotid plaques are increasingly recognized as a potential mechanism for ischemic stroke. We assessed the prevalence of such plaques in patients with low-risk neurologic events and evidence of DWI (Diffusion Weighted Imaging)-positive ischemia., Methods: This is a post-hoc exploratory analysis from the DOUBT study, a prospective, observational, multicenter study of patients with low-risk transient or persistent minor focal neurological symptoms. Patients who had baseline CT angiography (CTA) and an MRI within 8 days of their event were included in the study. We aimed to assess the prevalence of non-stenotic carotid disease in patients with versus without DWI-positive events, and in patients with ipsilateral DWI-positive events. A carotid-level analysis with univariable logistic regression analysis was performed to assess whether any of the assessed plaque features were associated with ipsilateral stroke., Results: Of the 334 patients (mean age 62.7 years, 50.4% females) with available vascular neuroimaging, 153 (45.9%) had non-stenotic carotid plaques (≤50% stenosis), 174 (52.1%) had no stenosis and 7 (2.1%) patients had >50% stenosis. Of those with non-stenotic carotid plaques, 31/153 (20.3%) had evidence of DWI-positive ischemia, approximately half (15/31; 48.4%) of which was in the territory of the carotid plaque. Amongst patients with DWI-positive ischemia, non-stenotic plaques were significantly more common on the side of DWI-positive lesions [31/49 (63.3%) versus 18/49(36.7%)]. Presence of non-stenotic plaque was a risk marker for DWI-positive events (RR 1.4, 95% CI 1.1-1.8, p 0.012). On matched analysis, non-stenotic plaques were more likely on the side of DWI+ ischemia (odds ratio 1.14, 95% CI 0.36-3.70, McNemar's p value 0.80). Plaque features, including hypodensity, irregularity and greater plaque thickness were significantly associated with a higher likelihood of ipsilateral DWI+ ischemia., Conclusion: In patients with low-risk transient or persistent neurologic events, non-stenotic carotid plaques are more common in patients with DWI-positive ischemia. Plaque features like hypodense and irregular plaque were more common with DWI-positive changes in the territory of the affected carotid., Competing Interests: Conflict of interest: F. Bala: is supported by La Société Française de Neuroradiologie et La Société Française de Radiologie. F. Moreau: reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study; and receiving grants from the Canadian Stroke Consortium outside the submitted work. T.S. Field: is supported by a Sauder Family/Heart and Stroke Foundation Professorship of Stroke Research. She discloses advisory board work for Bayer, Novartis, HLS Therapeutics and AstraZeneca, expert witness testimony (plaintiff and defendant) and is on the board of DESTINE Health. M. Goyal: Reports personal fees from Mentice, Medtronic, Microvention, and Stryker outside the submitted work; in addition, Dr Goyal has a patent to systems of acute stroke diagnosis issued and licensed. M.D. Hill: reported receiving grants from Medtronic, Boehringer Ingelheim, and NoNO Inc outside the submitted work. S.B. Coutts: receives study drug from Boehringer Ingelheim. M. Almekhlafi, N. Singh and DOUBT study investigators declare that they have no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Intracranial aneurysm (IA) poses significant health risks, yet the specific mRNA profiles and regulatory mechanisms distinguishing unruptured IA (UIA) from ruptured IA (RIA) remain unclear. This study aimed to elucidate these differences through comprehensive mRNA analysis. We employed RNA sequencing to compare mRNA expression patterns among control individuals, UIA patients, and RIA patients. Differential expression analysis identified triggering receptor expressed on myeloid cells 1 (TREM1) as a potential biomarker for IA occurrence and rupture, which was validated in an expanded cohort. In vitro experiments revealed that TREM1 overexpression in human umbilical vein endothelial cells (HUVECs) inhibited proliferation, angiogenesis, and migration while promoting apoptosis and inflammation. Bioinformatic predictions and subsequent chromatin immunoprecipitation assays confirmed signal transducer and activator of transcription 1 (STAT1) as a transcriptional regulator of TREM1. STAT1 overexpression in HUVECs activated the MAPK signaling pathway and mimicked the effects of TREM1 overexpression, which were reversible by TREM1 inhibition. Conversely, P38 MAPK inhibition produced opposite effects, which were negated by STAT1 overexpression. This study identifies TREM1 as a potential biomarker for IA occurrence and rupture, likely regulated by STAT1, offering new avenues for non-invasive IA intervention strategies., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical Approval: The study received approval from the ethics committee of Anhui Provincial Hospital and adhered to the principles of the Declaration of Helsinki. Informed consent was obtained from all participants, and written consent was specifically obtained from the parents of participants. It is important to note that no minors were included in this study., (© 2024. The Author(s).)

Purpose: Here we assess whether the volume of cerebral ischemia induced during glioma surgery may negatively impact survival independently of neurological function. We also evaluate the sensitivity of intraoperative MRI (iMRI) in detecting cerebral ischemia during surgery., Methods: We retrospectively reviewed 361 cranial surgeries that used a 3 Tesla iMRI. 165 patients met all inclusion criteria and were included in the final analysis. Diffusion weighted imaging (DWI) obtained during iMRI was compared to postoperative DWI obtained within 7 days of the operation in cases where no further resection occurred after the iMRI., Results: 42 of 165 patients (25%) showed at least some evidence of restricted diffusion on postoperative (poMRI). 37 of these 42 (88%) cases lacked evidence of restricted diffusion on iMRI, meaning iMRI had a false-negative rate of 88% and a sensitivity of 12% in assessing the extent of ischemic brain after surgery. In high-grade gliomas, the volume of restricted diffusion on poMRI was predictive of overall survival, independent of new functional deficits acquired during surgery (p = 0.011)., Conclusion: This study presents the largest case series to date analyzing the sensitivity of iMRI in detecting surgical ischemia. In high-grade gliomas, increased volume of ischemia correlated with worsening median overall survival (OS) irrespective of postoperative neurologic deficits. Future work will focus on improving intraoperative detection of ischemia during the hyperacute phase when interventions such as blood pressure modulation or direct application of vasodilator agents may be effective., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country., Methods: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart-Lung Transplantation., Results: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32)., Conclusions: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Introduction: The percentage of low attenuation area (%LAA) on computed tomography (CT) is useful for evaluating lung emphysema, and higher %LAA was observed in patients with chronic lung allograft dysfunction (CLAD). This study investigated the relationship between the %LAA and the development of CLAD after bilateral lung transplantation (LT). Methods: We conducted a single‐center retrospective study of 75 recipients who underwent bilateral LT; the recipients were divided into a CLAD group (n = 30) and a non‐CLAD group (n = 45). The %LAA was calculated using CT and compared between the two groups from 4 years before to 4 years after the diagnosis of CLAD. The relationships between the %LAA and the percent baseline values of the pulmonary function test parameters were also calculated. Results: The %LAA was significantly higher in the CLAD group than in the non‐CLAD group from 2 years before to 2 years after the diagnosis of CLAD (P <.05). In particular, patients with bronchiolitis obliterans syndrome (BOS) exhibited significant differences even from 4 years before to 4 years after diagnosis (P <.05). Significant negative correlations between the %LAA and the percent baseline values of the forced expiratory volume in 1 s (r = −.36, P =.0031), the forced vital capacity (r = −.27, P =.027), and the total lung capacity (r = −.40, P <.001) were seen at the time of CLAD diagnosis. Conclusion: The %LAA on CT was associated with the development of CLAD and appears to have the potential to predict CLAD, especially BOS, after bilateral LT. [ABSTRACT FROM AUTHOR]

Tryptophan (Trp) is an essential proteinogenic amino acid and metabolic precursor for several signaling molecules that has been implicated in many physiological and pathological processes. Since the two main branches of Trp metabolism—serotonin biosynthesis and kynurenine pathway—are differently affected by a variety of neurological and neoplastic diseases, selective visualization of these pathways is of high clinical relevance. However, while positron emission tomography (PET) with existing probes can be used for non-invasive assessment of total Trp metabolism, optimal imaging agents for pathway-specific PET imaging are still lacking. In this work, we describe the preparation of two 18F-labeled Trp derivatives, NIn-methyl-6-[18F]fluorotryptophan (NIn-Me-6-[18F]FTrp) and 5-hydroxy-7-[18F]fluorotryptophan (5-HO-7-[18F]FTrp). We also report feasible synthetic routes for the preparation of the hitherto unknown boronate radiolabeling precursors and non-radioactive reference compounds. Under optimized conditions, alcohol-enhanced Cu-mediated radiofluorination of the respective precursors afforded NIn-Me-6-[18F]FTrp and 5-HO-7-[18F]FTrp as application-ready solutions in radiochemical yields of 45 ± 7% and 29 ± 4%, respectively. As such, our work provides access to two promising candidate probes for pathway-specific visualization of Trp metabolism in amounts sufficient for their preclinical evaluation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the transport capability of nicotine across Calu-3 cell monolayer in various nicotine forms, including nicotine freebase, nicotine salts, and flavored e-liquids with nicotine benzoate. Significance: Nicotine is rapidly absorbed from the respiratory system into systemic circulation during e-cigarettes use. However, the mechanism of nicotine transport in the lung has not been well understood yet. This study may offer critical biological evidence and have implications for the use and regulation of e-cigarettes. Methods: The viability of Calu-3 cells after administration of nicotine freebase, nicotine salts and representative e-liquid were evaluated using the MTT assay, and the integrity of the Calu-3 cell monolayer was evaluated by transepithelial electrical resistance measurement and morphological analysis. Further, the nicotine transport capacity across the Calu-3 cell monolayer in various formulations of nicotine was investigated by analysis of nicotine transport amount. Results: The findings indicated that nicotine transport occurred passively and was time-dependent across the Calu-3cell monolayer. In addition, the nicotine transport was influenced by the type of nicotine salts and their respective pH value. The nicotine benzoate exhibited the highest apparent permeability coefficient (Papp), and higher nicotine-to-benzoic acid ratios led to higher Papp values. The addition of flavors to e-liquid resulted in increased Papp values, with the most significant increment being observed in tobacco-flavored e-liquid. Conclusions: In summary, the transport capability of nicotine across the Calu-3 cell monolayer was influenced by the pH values of nicotine salts and flavor additives in e-liquids. [ABSTRACT FROM AUTHOR]

Nicotine lactate, nicotine tartrate, nicotine benzoate, and freebase nicotine (FBN) are four forms of nicotine salt systems that are present in tobacco products. However, few in vivo studies have compared their pharmacological (pK) efficacies, which are important for understanding their roles in the addiction and abuse of tobacco and nicotine products. In this work, the pK of the above nicotine salt systems was studied by subcutaneously injecting their aqueous solutions in rats and obtaining blood samples from the jugular vein. Nicotine levels in the blood were analyzed by LC–MS/MS. The results demonstrated that rapid nicotine absorption occurred in all nicotine systems. Of them, NB had the smallest Tmax, while FBN had the largest Tmax. The nicotine metabolic rate and clearance decreased for FBN, indicating that nicotine retention in the body was higher than for the other three salt‐based systems. Compared with nicotine salts, FBN could reach and maintain a higher concentration in the animal model. Additionally, as the benzoic acid ratios increased, the Cmax of the nicotine benzoate (NB) in the plasma decreased. This indicates that the lower the pH, the lower the Cmax. When different concentrations of NB were used, the higher the NB concentration, the greater the Cmax and AUC(0‐t). These results demonstrate that nicotine adsorption by NB in the animal model depended on both pH and concentration. This baseline information could be used to explain different clinical pharmacological observations in humans, though this study only considered the effects of nicotine on pharmacokinetics in vivo. [ABSTRACT FROM AUTHOR]

There are different forms of nicotine in tobacco and tobacco products, and the differences in their contents significantly impact tobacco products. Based on a brief review of nicotine forms, the research on the differences in the release and physiological effects of different forms of nicotine is reviewed. It pointed out that: due to differences in physicochemical properties, freebase nicotine in tobacco products is more easily released into the aerosol; in terms of sensory effects and freebase nicotine is more irritating, and nicotine salts are relatively softer; in terms of absorption rate, due to the existence of multiple modes of administration, the absorption rate of different forms of nicotine exists in terms of toxicity, free nicotine is generally less toxic than nicotine salts, but the toxicity of nicotine salts varies depending on the type of acid ions; in terms of addictiveness, nicotine salts may be more addictive than free nicotine and may vary depending on the type of acid ions. In the future, the differences in ab- sorption rate, toxicity and addictive physiological effects of freebase nicotine and nicotine salts and their potential mechanisms should be thoroughly investigated to better guide the application of nicotine salts in tobacco products. [ABSTRACT FROM AUTHOR]

Aluminum foam is expected to be one of the candidates for lightweight materials for structural components as it is lightweight and has excellent shock absorption and sound absorption properties. However, aluminum foam has low tensile and flexural strength due to its thin cell walls. Therefore, aluminum foam is used by combining with dense materials. In particular, with the recent trend toward multi-materials, research on the combination with lightweight resins is expected. In this study, we attempted to join aluminum foam fabricated by the precursor method to a thermoplastic resin polycarbonate (PCTA) plate by friction welding. It was found that the aluminum foam and PCTA plate can be joined in about 1 min by friction welding, by rotating the aluminum foam at 2000 rpm and pressing 1 mm into the PCTA plate. In addition, in the friction welding of aluminum foam and PCTA plate, it was found that the pores of the aluminum foam were maintained without being collapsed. The anchoring effect is presumably caused by the penetration of PCTA softened by the frictional heat generated by the friction welding into the pores. Furthermore, tensile tests of the joined samples showed that fracture occurred either at the joining interface or at the base material of the aluminum foam, and that the joining strength was equivalent to the tensile strength of the aluminum foam itself. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a significant cause of cancer-related mortality, and triple-negative breast cancer (TNBC) is a particularly aggressive subtype associated with high mortality rates, especially among younger females. TNBC poses a considerable clinical challenge due to its aggressive tumor behavior and limited therapeutic options. Aberrations within the PI3K/AKT pathway are prevalent in TNBC and correlate with increased therapeutic intervention resistance and poor outcomes. MicroRNAs (miRs) have emerged as crucial PI3K/AKT pathway regulators influencing various cellular processes involved in TNBC pathogenesis. The levels of miRs, including miR-193, miR-4649-5p, and miR-449a, undergo notable changes in TNBC tumor tissues, emphasizing their significance in cancer biology. This review explored the intricate interplay between miR variants and PI3K/AKT signaling in TNBC. The review focused on the molecular mechanisms underlying miR-mediated dysregulation of this pathway and highlighted specific miRs and their targets. In addition, we explore the clinical implications of miR dysregulation in TNBC, particularly its correlation with TNBC prognosis and therapeutic resistance. Elucidating the roles of miRs in modulating the PI3K/AKT signaling pathway will enhance our understanding of TNBC biology and unveil potential therapeutic targets. This comprehensive review aims to discuss current knowledge and open promising avenues for future research, ultimately facilitating the development of precise and effective treatments for patients with TNBC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Arteriovenous fistulas (AVFs) adjacent to the clivus, such as cavernous sinus dural AVFs (CSDAVFs) and condylar AVFs, sometimes have an intraosseous shunted pouch and recruit blood supply from transosseous feeders. Precise analysis of transosseous feeders regarding the clival lesion has not yet been performed. Therefore, this study aimed to clarify the characteristics and identity of transosseous feeders in clival lesions. Methods: Patients with CSDAVFs and condylar AVFs, who underwent high-resolution cone-beam computed tomography or three-dimensional rotational angiography in our institute, were included. The frequency, type of branch, penetrating point, and termination of intraosseous feeders were retrospectively evaluated. Results: A total of 31 patients with 36 lesions in CSDAVFs and 8 patients with 8 lesions in condylar AVFs underwent angiography. For CSDAVFs, 38 transosseous feeders were detected in 23 out of 31 patients, including 22 in the pharyngeal branch of the ascending pharyngeal artery (APhA), 6 in the hypoglossal branch of the APhA, 6 in the accessory meningeal artery, 3 in the meningohypophyseal trunk (MHT), and 1 in the anterior branch of the middle meningeal artery. For condylar AVFs, 24 transosseous feeders were detected in all 8 patients, including 11 in the pharyngeal branches of the APhA, 7 in the hypoglossal branch of the APhA, 6 in the segmental artery from the vertebral artery, and 2 in the MHT. Conclusion: Transosseous feeders of AVFs around the clivus, which are frequently seen in AVFs of this area, mainly arise from ventral clival branches and from pharyngeal branches of the APhA. [ABSTRACT FROM AUTHOR]

Conceptually, a wide beneficial effect, both peripherally and centrally, might have been essential for the harmony of brain–gut and gut–brain axes' function. Seen from the original viewpoint of the gut peptides' significance and brain relation, the favorable stable gastric pentadecapeptide BPC 157 evidence in the brain–gut and gut–brain axes' function might have been presented as a particular interconnected network. These were the behavioral findings (interaction with main systems, anxiolytic, anticonvulsive, antidepressant effect, counteracted catalepsy, and positive and negative schizophrenia symptoms models). Muscle healing and function recovery appeared as the therapeutic effects of BPC 157 on the various muscle disabilities of a multitude of causes, both peripheral and central. Heart failure was counteracted (including arrhythmias and thrombosis), and smooth muscle function recovered. These existed as a multimodal muscle axis impact on muscle function and healing as a function of the brain–gut axis and gut–brain axis as whole. Finally, encephalopathies, acting simultaneously in both the periphery and central nervous system, BPC 157 counteracted stomach and liver lesions and various encephalopathies in NSAIDs and insulin rats. BPC 157 therapy by rapidly activated collateral pathways counteracted the vascular and multiorgan failure concomitant to major vessel occlusion and, similar to noxious procedures, reversed initiated multicausal noxious circuit of the occlusion/occlusion-like syndrome. Severe intracranial (superior sagittal sinus) hypertension, portal and caval hypertensions, and aortal hypotension were attenuated/eliminated. Counteracted were the severe lesions in the brain, lungs, liver, kidney, and gastrointestinal tract. In particular, progressing thrombosis, both peripherally and centrally, and heart arrhythmias and infarction that would consistently occur were fully counteracted and/or almost annihilated. To conclude, we suggest further BPC 157 therapy applications. [ABSTRACT FROM AUTHOR]

Inositol is closely related to the occurrence of neural tube defects (NTDs). Inositol 1, 3, 4-trisphosphate 5/6-kinase (ITPK1) gene encoded an essential regulatory enzyme ITPK1, which is involved in inositol metabolism and has a critical role in the development of neural tube and axial mesoderm. It had been reported that some polymorphisms of critical genes in inositol pathways, including ITPK1, were associated with NTDs in Chinese pregnant women; however, the association between fetus ITPK1 polymorphisms and NTDs had not been reported. In a high incidence of NTDs region of China, a case–control study was performed to evaluate the association between fetal ITPK1 polymorphisms and NTDs. The ITPK1 polymorphisms were genotyped by iPLEX® Gold assay. Inositol levels in fetus brain tissues were analyzed. Three genetic polymorphisms of fetus ITPK1's, including rs3818175, rs2295394, and rs4586354, were statistically associated with spina bifida (NTD subtypes). A higher risk of spina bifida was associated with genotype GG of rs3818175, genotype CC of rs4586354, and genotype TT of rs2295394 (OR = 2.66, 95% CI [1.17–6.05], P = 0.017; OR = 2.22, 95% CI [1.02–4.80], P = 0.041; and OR = 2.33, 95% CI [1.00–5.48], P = 0.047), when compared with the other wild-type genotypes CC, TT, and CC, respectively. Decreased brain inositol level was found in NTDs fetuses, compared to normal controls. Inositol levels were found to significantly decrease with rs2295394 (CC genotype), rs4586354 (TT genotype), and rs3818175 (GC genotype) (P < 0.05). The polymorphisms of fetus ITPK1 were associated with the incidence of NTDs and might be a genetic risk factor for spina bifida. [ABSTRACT FROM AUTHOR]

With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non‐invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [15O]H2O and [18F]FDG. Despite the success of these techniques, it became apparent that more specific probes were needed to understand the neurochemical bases of psychiatric disorders. The first neurochemical PET imaging probes targeted sites of action of neuroleptic (dopamine D2 receptors) and psychoactive (serotonin receptors) drugs. Based on the centrality of monoamine dysfunction in psychiatric disorders and the measured success of monoamine‐enhancing drugs in treating them, the next 30 years witnessed the development of an armamentarium of PET radiopharmaceuticals and imaging methodologies for studying monoamines. Continued development of monoamine‐enhancing drugs over this time however was less successful, realizing only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely paralleled drug development priorities resulting in the development of new PET imaging agents for non‐monoamine targets. Part one of this review will briefly survey novel PET imaging targets with relevance to the field of psychiatry, which include the metabotropic glutamate receptor type 5 (mGluR5), purinergic P2X7 receptor, type 1 cannabinoid receptor (CB1), phosphodiesterase 10A (PDE10A), and describe radiotracers developed for these and other targets that have matured to human subject investigations. Current limitations of the targets and techniques will also be discussed. [ABSTRACT FROM AUTHOR]

Moyamoya disease is often diagnosed after intracranial hemorrhage in adult patients. Here, we report a case of unilateral moyamoya disease treated with indirect revascularization combined with cranioplasty after treatment for acute subdural hematoma and subcortical hemorrhage. A middle-aged woman with disturbed consciousness was transferred to our hospital. Computed tomography (CT) revealed an acute subdural hematoma with left temporoparietal subcortical hemorrhage. Three-dimensional CT angiography indicated a scarcely enhanced left middle cerebral artery (MCA) that was suspected to be delayed or nonfilling due to increased intracranial pressure. Subsequently, hematoma evacuation and external decompression were performed. Postoperative digital subtraction angiography (DSA) revealed stenosis of the left MCA and moyamoya vessels, indicating unilateral moyamoya disease. Forty-five days after the initial procedure, we performed encephalo-arterio-synangiosis (EAS) using the superficial temporal artery simultaneously with cranioplasty for the skull defect. The modified Rankin Scale score of the patient one year after discharge was 1, and the repeat DSA showed good patency of the EAS. Revascularization using EAS in the second step can be an option for revascularization for hemorrhagic moyamoya disease if the patient required cranioplasty for postoperative skull defect after decompressive craniotomy. [ABSTRACT FROM AUTHOR]

Background: Intracranial dural arteriovenous fistulas (DAVFs) have been documented to occasionally spontaneously regress. However, the mechanism responsible for this occurrence remains speculative. Methods: We present a case of a Borden II - Cognard IIa+b DAVF involving the superior sagittal sinus (SSS) with bilateral external carotid artery supply that regressed spontaneously. A systematic literature review was conducted to explore the current theories explaining the spontaneous regression of DAVFs according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Results: A total of 26 studies and 54 cases were included in our results. Of the included cases, 57.14% of cases were Borden I, 16.33% were Borden II, and 26.53% were Borden III. Ruptured status or intracranial hemorrhage was documented in 24.1% of all cases, the majority of which (69.2%) were in cases with aggressive lesions (Borden II or greater). The most commonly involved location was the transverse sinus (38.89% of cases, n = 21), and the SSS was only involved in 12.96% of all cases. 50% of included cases proposed a mechanism responsible for spontaneous regression. The most frequently proposed mechanisms were thrombosis of the involved sinus/chronic inflammatory changes or direct endothelial injury, endoluminal stasis, and thrombogenic effects of contrast medium during angiography. We present the case of a 54-year-old woman with an aggressive ruptured DAVF that likely developed following a pediatric traumatic brain injury that was left untreated before she presented to our institution after significant delay. Her DAVF regressed on repeat angiography before neurovascular intervention without a clear identifying mechanism as proposed by the current literature. Conclusion: Our results suggest that spontaneous regression is not necessarily associated with lower risk DAVFs. The present case offers a unique long-term insight into the natural history of an aggressive ruptured DAVF of the SSS that regressed without intervention. Further research into the natural history of DAVFs will be helpful in deducing key factors leading to spontaneous regression. [ABSTRACT FROM AUTHOR]

Background: Dural arteriovenous fistulas (dAVFs) occurring near the hypoglossal canal are rare. Detailed evaluation of vascular structures can identify shunt pouches at the jugular tubercle venous complex (JTVC) in the bone near the hypoglossal canal. Although the JTVC has several venous connections, including the hypoglossal canal, there have been no reports of transvenous embolization (TVE) of a dAVF at the JTVC using an approach route other than the hypoglossal canal. This report describes the first case of complete occlusion with targeted TVE using an alternative approach route in a 70-year-old woman presenting with tinnitus diagnosed with dAVF at the JTVC. Case Description: The patient had no history of head trauma or other preexisting conditions. Magnetic resonance imaging (MRI) showed no abnormal findings in the brain parenchyma. Magnetic resonance angiography (MRA) revealed a dAVF near the ACC. The shunt pouch was located in the JTVC, near the left hypoglossal canal, with feeders from the bilateral ascending pharyngeal arteries and occipital arteries, left meningohypophyseal trunk, and odontoid arch of the left vertebral artery. TVE was performed near the shunt pouch. Localized packing of the shunt point was achieved. The patient's tinnitus improved. Postoperative MRI showed disappearance of the shunt without any complications. No recurrence was observed on MRA 6 months after treatment. Conclusion: Our results suggest targeted TVE is an effective treatment for dAVFs at the JTVC. [ABSTRACT FROM AUTHOR]

Objectives: We herein review the outcomes of paediatric lung transplantation (LTx) and analyse subgroups divided by age. Methods: We retrospectively reviewed 43 consecutive paediatric LTx recipients (< 18 years old: cadaveric LTx [n = 9], living-donor lobar LTx [n = 34]). We also analysed subgroups of patients 1–6 years old (n = 10) and 7–17 years old (n = 33). Results: The 1-, 5- and 10-year overall survival (OS) rates in paediatric recipients were 93%, 82% and 67%, respectively. The 1-, 5- and 10-year graft dysfunction (GD)-free survival rates in paediatric recipients were 85%, 59% and 31%, respectively. The 1- and 5-year OS in the 1- to 6-year-old vs. 7- to 17-year-old groups were 70% vs. 100% and 48% vs. 93%, respectively (p < 0.0001). The 1- and 5-year GD-free survival rates in the 1- to 6-year-old vs. 7- to 17-year-old groups were 60% vs. 93% and 24% vs. 69%, respectively (p = 0.024). The 1- to 6-year-old group showed higher rates of non-standard LTx (p = 0.0001), interstitial pneumonia (p = 0.004) and ventilator dependency (p = 0.007) than the 7- to 17-year-old group. Conclusion: Paediatric recipients under 7 years old seemed to have a higher risk of mortality and GD than those 7 years old and older. [ABSTRACT FROM AUTHOR]

Biological mediators secreted during peripheral chronic inflammation reach the bloodstream and may damage the blood–brain barrier (BBB), triggering central nervous system (CNS) disorders. Full-fledged human BBB models are efficient tools to investigate pharmacological pathways and mechanisms of injury at the BBB. We here employed a human in vitro BBB model to investigate the effects of either plasma from inflammatory bowel disease (IBD) patients or tumor necrosis factor α (TNFα), a cytokine commonly released in periphery during IBD, and the anti-inflammatory role of pioglitazone, a peroxisome proliferator-activated receptor γ agonist (PPARγ). The BBB model was treated with either 10% plasma from healthy and IBD donors or 5 ng/mL TNFα, following treatment with 10 µM pioglitazone. Patient plasma did not alter BBB parameters, but TNFα levels in plasma from all donors were associated with varying expression of claudin-5, claudin-3 and ICAM-1. TNFα treatment increased BBB permeability, claudin-5 disarrangement, VCAM-1 and ICAM-1 expression, MCP1 secretion and monocyte transmigration. These effects were attenuated by pioglitazone. Plasma from IBD patients, which evoked higher BBB permeability, also increased ICAM-1 expression, this effect being reversed by pioglitazone. Our findings evidence how pioglitazone controls periphery-elicited BBB inflammation and supports its repurposing for prevention/treating of such inflammatory conditions. [ABSTRACT FROM AUTHOR]

Recent research has acknowledged young children's potential to engage in data handling activities and create their own representations. However, our knowledge on children's graphical signs produced during data representations and the way they are utilized is poor. Highlighting the critical importance of signs as cultural tools for mathematical learning, this study focused on the components of the original data representations which emerged from child-initiated data investigations. Analysis of children's artefacts revealed five kinds of inscriptions and four kinds of information included in their data representations. The insightful way of utilizing their inscriptions demonstrated how the young learners, apart from inventing their own graphical signs, adapted broadly accepted symbols to the contextual and communicational requirements of their inquiries and made them part of their personal toolkit for handling data tasks. These aspects of their meta-representational knowledge are discussed through a sociocultural lens, while implications for research and practice are also suggested. [ABSTRACT FROM AUTHOR]

Abnormalities in type I procollagen genes (COL1A1 and COL1A2) are responsible for hereditary connective tissue disorders including osteogenesis imperfecta (OI), specific types of Ehlers‐Danlos syndrome (EDS), and COL1‐related overlapping disorder (C1ROD). C1ROD is a recently proposed disorder characterized by predominant EDS symptoms of joint and skin laxity and mild OI symptoms of bone fragility and blue sclera. Patients with C1ROD do not carry specific variants for COL1‐related EDS, including classical, vascular, cardiac‐valvular, and arthrochalasia types. We describe clinical and molecular findings of 23 Japanese patients with pathogenic or likely pathogenic variants of COL1A1 or COL1A2, who had either OI‐like or EDS‐like phenotypes. The final diagnoses were OI in 17 patients, classical EDS in one, and C1ROD in five. The OI group predominantly experienced recurrent bone fractures, and the EDS group primarily showed joint hypermobility and skin hyperextensibility, though various clinical and molecular overlaps between OI, COL1‐related EDS, and C1ROD as well as intrafamilial phenotypic variabilities were present. Notably, life‐threatening vascular complications (vascular dissections, arterial aneurysms, subarachnoidal hemorrhages) occurred in seven patients (41% of those aged >20 years) with OI or C1ROD. Careful lifelong surveillance and intervention regarding bone and vascular fragility could be required. [ABSTRACT FROM AUTHOR]

Moyamoya disease is a medical condition that shows the typical characteristics like continuous and chronic thickening of the walls and the contraction of the internal carotid artery; as a result, the internal diameter of the artery gets narrowed. There are six phases of the disease ranging from I to VI (moyamoya vessels completely disappear, followed by the complete blockage of the arteries). Surgery is a commonly recommended treatment for the moyamoya disease. Our research study identifies the effect of autologous bone marrow stem cell therapy (ABMSCT) on the levels of inflammatory factors and Conexin43 (Cx43) protein in patients suffering from moyamoya. In our study, we have selected 52 moyamoya patients admitted to our hospital from 30 July 2019 to 10 February 2020. The control group (CG) was treated with superficial temporal artery to a middle cerebral artery (STA-MCA) bypass + encephalo-duro-myosinangiosis (EDMS). The experimental group (Exp. Grp) was treated with ABMSC. The cerebral vascular tissue of the patients was treated with hematoxylin-eosin (HE) staining. Immunohistochemical staining was used to identify the levels of Cx43 protein. The concentrations of vascular endothelial growth factor (VEGF), inflammatory factor interleukin-6 (IL6), interleukin-1β (IL1β), tumor necrosis factor (TNFα), and anti-inflammatory factor interleukin-1β (IL1β) were determined by enzyme-linked immunosorbent assay (ELISA). We have found that after treatment of the expression of Cx43 protein, the proportions of grade IV (7.7%), grade III (311.5%), and grade II (3.8%) patients in the Exp. Grp were lower than those in the CG. The proportion of grade I patients in the Exp. Grp (77%) was higher than that in the CG (38.5%). After treatment, the inflammatory factors IL6 (0.97 ± 0.82 pg/mL), IL1β (8.33 ± 1.21 pg/mL), and TNFα (1.73 ± 0.71 pg/mL) in the Exp. Grp were lower than those in the CG. The anti-inflammatory factor IL1β (15.09 ± 4.72 pg/mL) increased in the Exp. Grp compared with the CG (11.25 ± 3.48 pg/mL) post treatment. Intracranial infection, hydrocephalus, hemiplegia, and transient neurological dysfunction in the Exp. Grp were lower than those in the CG, with statistical differences P < 0.05 . Our study suggests that the treatment of autologous bone marrow stem cells (ABMSC) was beneficial to balance the inflammatory response of disorders, reduce the damage of vascular tissue in the brain, and regulate tissue repair by co-acting with various inflammatory factors as compared to traditional surgery. We conclude that the involvement of Cx43 in the occurrence and development of moyamoya. We also have found that the risk factors of intracranial infection after ABMSCT were less as compared to those after conventional surgery. [ABSTRACT FROM AUTHOR]

Objective: To explore whether deep medullary veins (DMVs) in the unaffected hemisphere were associated with functional outcome in acute cardioembolic stroke patients. Methods: Acute cardioembolic stroke patients at a single center were retrospectively included. DMVs visibility in the unaffected hemisphere was assessed using a well-established four-grade scoring method based on susceptibility-weighted imaging (SWI): grades 0–3 (grade 0 for no visible DMVs; grade 1 for the numbers of conspicuous DMVs < 5; grade 2 for numbers raging from 5 to 10; grade 3 for more than 10). Patients were further divided into mild-to-moderate (grade 0–2) and severe DMVs (grade 3) groups. Functional outcomes were evaluated using the modified Rankin scale (mRS) score at three months. Poor outcome was defined as mRS ≥ 3. Binary logistic regression analysis was used to explore the association between DMVs grade and functional outcome. Results: A total of 170 patients were finally included. Compared with the mild-to-moderate DMVs group (149 patients), the severe DMVs group (21 patients) had higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.002), lower levels of admission systolic blood pressure (BP) (p = 0.031), and elevated rates of large infarction (p = 0.003). At three months, the severe DMVs group had higher mRS (p = 0.002). Patients in the poor outcome group (82/170, 48.2%) had older age, higher baseline NIHSS score, lower admission diastolic BP, higher rates of hemorrhagic transformation and large infarction, and an increased proportion of severe DMVs (all p < 0.05). After adjusting for confounders, multivariable regression analysis showed that the severe DMVs grade (adjusted odds ratio [OR] = 5.830, 95% confidence interval [CI] = 1.266–26.856, p = 0.024) was significantly associated with three-month functional outcomes without interaction with other potential risk factors (p for interaction > 0.05). Conclusions: DMVs grade in the unaffected hemisphere was independently associated with three-month functional outcome in acute cardioembolic stroke patients. Patients with severe DMVs were more likely to have a poor functional outcome at three months. [ABSTRACT FROM AUTHOR]

Introduction. Standard neuroimaging protocols for brain tumors have well-known limitations. The clinical use of additional modalities including amino acid PET (aaPET) and advanced MRI (aMRI) techniques (including DWI, PWI, and MRS) is emerging in response to the need for more accurate detection of brain tumors. In this systematic review of the past 2 years of the literature, we discuss the most recent studies that directly compare or combine aaPET and aMRI for brain tumor imaging. Methods. A PubMed search was conducted for human studies incorporating both aaPET and aMRI and published between July 2018 and August 2020. Results. A total of 22 studies were found in the study period. Recent studies of aaPET with DWI showed a superiority of MET, FET, FDOPA, and AMT PET for detecting tumor, predicting recurrence, diagnosing progression, and predicting survival. Combining modalities further improved performance. Comparisons of aaPET with PWI showed mixed results about spatial correlation. However, both modalities were able to detect high-grade tumors, identify tumor recurrence, differentiate recurrence from treatment effects, and predict survival. aaPET performed better on these measures than PWI, but when combined, they had the strongest results. Studies of aaPET with MRS demonstrated that both modalities have diagnostic potential but MET PET and FDOPA PET performed better than MRS. MRS suffered from some data quality issues that limited analysis in two studies, and, in one study that combined modalities, overall performance actually decreased. Four recent studies compared aaPET with emerging MRI approaches (such as CEST imaging, MR fingerprinting, and SISTINA), but the initial results remain inconclusive. Conclusions. aaPET outperformed the aMRI imaging techniques in most recent studies. DWI and PWI added meaningful complementary data, and the combination of aaPET with aMRI yielded the best results in most studies. [ABSTRACT FROM AUTHOR]

Metastasis is a leading cause of mortality and poor prognosis in colorectal cancer (CRC). Thus, the identification of new compounds targeting cell migration represents a major clinical challenge. Recent findings evidenced a central role for dysregulated Notch in CRC and a correlation between Notch overexpression and tumor metastasis. MicroRNAs (miRNAs) have been reported to cross-talk with Notch for its regulation. Therefore, restoring underexpressed miRNAs targeting Notch could represent an encouraging therapeutic approach against CRC. In this context, S-adenosyl-L-methionine (AdoMet), the universal biological methyl donor, being able to modulate the expression of oncogenic miRNAs could act as a potential antimetastatic agent. Here, we showed that AdoMet upregulated the onco-suppressor miRNAs-34a/-34c/-449a and inhibited HCT-116 and Caco-2 CRC cell migration. This effect was associated with reduced expression of migration-/EMT-related protein markers. We also found that, in colorectal and triple-negative breast cancer cells, AdoMet inhibited the expression of Notch gene, which, by luciferase assay, resulted the direct target of miRNAs-34a/-34c/-449a. Gain- and loss-of-function experiments with miRNAs mimics and inhibitors demonstrated that AdoMet exerted its inhibitory effects by upregulating miRNAs-34a/-34c/-449a. Overall, these data highlighted AdoMet as a novel Notch inhibitor and suggested that the antimetastatic effects of AdoMet involve the miRNA-mediated targeting of Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Lung transplantation is the definitive therapy for patients living with end-stage lung disease. Despite significant progress made in the field, graft survival remains the lowest of all solid organ transplants. Additionally, the lung has among the lowest of organ utilization rates--among eligible donors, only 22% of lungs from multi-organ donors were transplanted in 2019. Novel strategies are needed to rehabilitate marginal organs and improve graft survival. Gene therapy is one promising strategy in optimizing donor allografts. Over-expression or inhibition of specific genes can be achieved to target various pathways of graft injury, including ischemic-reperfusion injuries, humoral or cellular rejection, and chronic lung allograft dysfunction. Experiments in animal models have historically utilized adenovirus-based vectors and the majority of literature in lung transplantation has focused on overexpression of IL-10. Although several strategies were shown to prevent rejection and prolong graft survival in preclinical models, none have led to clinical translation. The past decade has seen a renaissance in the field of gene therapy and two AAV-based in vivo gene therapies are now FDA-approved for clinical use. Concurrently, normothermic ex vivo machine perfusion technology has emerged as an alternative to traditional static cold storage. This preservation method keeps organs physiologically active during storage and thus potentially offers a platform for gene therapy. This review will explore the advantages and disadvantages of various gene therapy modalities, review various candidate genes implicated in various stages of allograft injury and summarize the recent efforts in optimizing donor lungs using gene therapy. [ABSTRACT FROM AUTHOR]

The hypoglossal canal (HC) is an unusual location of the posterior fossa dural arteriovenous fistula (AVF), which usually occurs in the transverse or sigmoid sinus. Herein, we report a case of HC dural AVF successfully treated with transvenous coil embolization using detachable coils in a 68-year-old woman who presented with headache and left pulsatile tinnitus for 2 months. Brain magnetic resonance imaging (MRI) and cerebral angiography revealed left HC dural AVF. The pulsatile bruit disappeared immediately after the procedure. Follow-up MRI showed complete disappearance of the fistula. Precise localization of the fistula through careful consideration of the anatomy and transvenous coil embolization using a detachable coil can facilitate the treatment for HC dural AVF. [ABSTRACT FROM AUTHOR]

Background: Endolymphatic sac tumour (ELST) is a rare low-grade locally aggressive neoplasm arising from the endolymphatic duct or sac. It presents mostly with vestibulo-cochlear symptoms either sporadically or as part of von Hippel–Lindau (VHL) syndrome. Micro-neurosurgical excision remains the cornerstone of therapy with the role of radiotherapy (RT) being controversial. This is a clinico-pathological analysis of consecutive ELST patients presenting to a single-institution in India. Methods: Neuropathology database of a tertiary-care comprehensive cancer centre was searched electronically to identify consecutive patients with histopathological diagnosis of ELST registered at the institute over last one decade. Data regarding demographic profile, clinical presentation, histopathological features, treatment details and outcomes were retrieved from electronic medical records for this retrospective analysis. Results: Electronic search identified seven unique patients with biopsy-proven ELST registered at the institute between 2009 and 2020. Median age of the study cohort was 39 years (range 24–65 years) with strong male predilection (5:2 ratio) and left-sided preponderance (71%). Most common presenting symptoms were hearing loss (86%) and earache (71%) on affected side followed by headache (43%). All patients underwent maximal safe resection at initial diagnosis and were followed-up closely with periodic surveillance imaging. Two patients underwent salvage RT using high-precision conformal techniques at recurrence/progression. Conclusion: ELST is a rare low-grade locally aggressive neoplasm that arises generally as part of VHL syndrome or sometimes sporadically. Gross total resection provides the best chance of cure with RT being reserved for unresectable disease, large residue, medical inoperability, or as salvage therapy for recurrent/progressive tumor. [ABSTRACT FROM AUTHOR]

Purpose: Decreased irisin levels may be associated with the development of emphysema. Similarly, emphysematous changes may develop in patients with chronic lung allograft dysfunction (CLAD) after living-donor lobar lung transplantation (LDLLT). We investigated the severity of emphysematous changes and the relationship between irisin levels and CLAD after bilateral LDLLT and cadaveric lung transplantation (CLT). Methods: The subjects of this retrospective study were 59 recipients of bilateral LDLLT (n = 31) or CLT (n = 28), divided into a non-CLAD group (n = 41), a LDLLT-CLAD group (n = 11), and a CLT-CLAD group (n = 7). We compared the severity of emphysematous changes, the skeletal muscle mass, and the plasma irisin levels among the groups. Results: The emphysematous changes were significantly more severe in the LDLLT-CLAD and CLT-CLAD groups (p = 0.046 and 0.036), especially in patients with bronchiolitis obliterans syndrome (BOS), than in the non-CLAD group. Although the skeletal muscle mass was similar in all the groups, the plasma irisin levels were significantly lower in the LDLLT-CLAD group (p = 0.022), especially in the patients with BOS after LDLLT, than in the non-CLAD group. Conclusion: Emphysematous changes and lower levels of plasma irisin were associated with CLAD, especially in patients with BOS, after bilateral LDLLT. [ABSTRACT FROM AUTHOR]

Access techniques for mechanical thrombectomy normally include percutaneous puncture of the common femoral or, more recently, the radial artery. Although target vessel catheterization may frequently not be devoid of difficulties via both routes, the vast majority of mechanical thrombectomy (MT) cases can be successfully managed. However, in a significant minority of cases, a stable target vessel access cannot be reached resulting in futile recanalization procedures and detrimental outcomes for the patients. As such, in analogy to direct carotid puncture for anterior circulation MT, direct vertebral artery (VA) puncture (DVP) is a direct cervical approach, which can constitute the only feasible access to the posterior circulation in highly selected cases. So far, due to the rarity of DVP, only anecdotal evidence from isolated case reports is available and this approach raises concerns with regard to safety issues, feasibility, and technical realization. We present a case in which bail-out access to the posterior circulation was successfully obtained through a roadmap-guided lateral direct puncture of the V2 segment of the cervical VA and give an overview of technical nuances of published DVP approaches for posterior circulation MT. [ABSTRACT FROM AUTHOR]

We aimed to investigate the efficacy of our multimodal strategies and propose a treatment algorithm for ruptured vertebral artery dissecting aneurysms (VADAs). This study included 41 patients treated at a single institution between 2015 and 2022. The treatment modalities were justified based on the collateral circulation and aneurysm location related to the posterior inferior cerebellar artery (PICA). Treatment outcomes and complications of each treatment group were analyzed. The association between the collateral blood flow and the postoperative vertebrobasilar ischemia (VBI) was also investigated. There were 17 post-PICA, 10 PICA-involved, 7 pre-PICA, and 7 non-PICA types. Reconstruction techniques included flow diversion devices (n = 11) and stent-assisted coiling (n = 3). Deconstruction techniques included coil trapping (n=17) and microsurgical parent artery occlusion with (n = 8) or without PICA revascularization (n = 2). Five (18.5%) of the deconstruction group had postoperative VBI. Overall favorable outcomes in both groups were observed in 70.7% of patients with a mean follow-up time of 21.5 months. Poor World Federation of Neurosurgical Societies grade (IV-V) was identified as a predictor of unfavorable outcomes (p = 0.003). In addition, the VA 4 /BA 4 ratio > 0.22, the presence of collateral blood flow from the posterior communicating artery (PcomA), and a contralateral VA diameter > 2.5 mm were associated with a lower risk of postoperative VBI. In summary, the proposed strategic treatment in this study is pragmatic, yielding satisfactory results where a deconstructive technique should be used with caution, particularly when there is a flow mismatch or the absence of collateral PcomA in the vertebrobasilar circulation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)