Congenital metastatic neuroblastoma with placental involvement as a rare cause of non-immune fetal hydrops.

Non-immune hydrops fetalis represents the end-stage status of a variety of diseases, including metastatic tumors. We report a case of non-immune hydrops fetalis associated with multiple disseminated echogenic nodular lesions detected by ultrasound and confirmed by magnetic resonance. Cordocentesis demonstrated anemia and thrombopenia. Differential diagnosis included histiocytosis X, acute leukemia or metastatic disease. A stillbirth was diagnosed at week 25 + 6. The autopsy revealed hydrops fetalis, a right adrenal gland mass, multiple disseminated nodules histologically composed of small round blue cells positive for synaptophysin, and placental involvement, concordant findings with congenital undifferentiated neuroblastoma Stage M. No chromosomal abnormalities were associated, nor amplification abnormalities in MYCN and ALK genes. Metastatic neuroblastoma should be considered in the differential diagnosis of non-immune hydrops fetalis associated with multiple nodular lesions.

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas.

Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune system against cancer has improved the survival rates dramatically in certain cancer types. Natural killer (NK) cells are a heterogeneous group of innate effector cells that possess numerous antitumor effects, such as cytolysis and cytokine production. Pediatric sarcoma cells have been shown to be especially susceptible to NK-cell-mediated killing. NK-cell adoptive therapy confers numerous advantages over T-cell adoptive therapy, including a good safety profile and a lack of major histocompatibility complex restriction. NK-cell immunotherapy has the potential to be a new therapy for pediatric malignant bone tumors. In this manuscript, we review the general characteristics of osteosarcoma and Ewing sarcoma, discuss the long-term effects of sarcoma treatment on bones, and the barriers to effective immunotherapy in bone sarcomas. We then present the laboratory and clinical studies on NK-cell immunotherapy for pediatric malignant bone tumors. We discuss the various donor sources and NK-cell types, the engineering of NK cells and combinatorial treatment approaches that are being studied to overcome the current challenges in adoptive NK-cell therapy, while suggesting approaches for future studies on NK-cell immunotherapy in pediatric bone tumors.

Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review.

The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood-nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.

Impact of GABAA and GABAB Inhibition on Cortical Dynamics and Perturbational Complexity during Synchronous and Desynchronized States.

Quantitative estimations of spatiotemporal complexity of cortical activity patterns are used in the clinic as a measure of consciousness levels, but the cortical mechanisms involved are not fully understood. We used a version of the perturbational complexity index (PCI) adapted to multisite recordings from the ferret (either sex) cerebral cortex in vitro (sPCI) to investigate the role of GABAergic inhibition in cortical complexity. We studied two dynamical states: slow-wave activity (synchronous state) and desynchronized activity, that express low and high causal complexity respectively. Progressive blockade of GABAergic inhibition during both regimes revealed its impact on the emergent cortical activity and on sPCI. Gradual GABAA receptor blockade resulted in higher synchronization, being able to drive the network from a desynchronized to a synchronous state, with a progressive decrease of complexity (sPCI). Blocking GABAB receptors also resulted in a reduced sPCI, in particular when in a synchronous, slow wave state. Our findings demonstrate that physiological levels of inhibition contribute to the generation of dynamical richness and spatiotemporal complexity. However, if inhibition is diminished or enhanced, cortical complexity decreases. Using a computational model, we explored a larger parameter space in this relationship and demonstrate a link between excitatory/inhibitory balance and the complexity expressed by the cortical network.SIGNIFICANCE STATEMENT The spatiotemporal complexity of the activity expressed by the cerebral cortex is a highly revealing feature of the underlying network's state. Complexity varies with physiological brain states: it is higher during awake than during sleep states. But it also informs about pathologic states: in disorders of consciousness, complexity is lower in an unresponsive wakefulness syndrome than in a minimally conscious state. What are the network parameters that modulate complexity? Here we investigate how inhibition, mediated by either GABAA or GABAA receptors, influences cortical complexity. And we do this departing from two extreme functional states: a highly synchronous, slow-wave state, and a desynchronized one that mimics wakefulness. We find that there is an optimal level of inhibition in which complexity is highest.

Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report.

Infantile fibrosarcoma (IFS) is a rare pediatric tumor which often presents the ETV6-NTRK3 gene fusion. NTRK3 encodes the neurotrophin-3 growth factor receptor tyrosine kinase, a druggable therapeutic target. Selective tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib, have shown efficacy and safety in the treatment of IFS. We report a case of an abdominal IFS diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects.

Calcium Dynamics and Synaptic Plasticity.

Synaptic plasticity is a fundamental property of neurons referring to the activity-dependent changes in the strength and efficacy of synaptic transmission at preexisting synapses. Such changes can last from milliseconds to hours, days, or even longer and are involved in learning and memory as well as in development and response of the brain to injuries. Several types of synaptic plasticity have been described across neuronal types, brain regions, and species, but all of them share in one way or another capital importance of Ca2+-mediated processes. In this chapter, we will focus on the Ca2+-dependent events necessary for the induction and expression of multiple forms of synaptic plasticity.

Extracellular adenosine reversibly inhibits the activation of human regulatory T cells and negatively influences the achievement of the operational tolerance in liver transplantation.

The artificial induction of tolerance in transplantation is gaining strength. In mice, a differential role of extracellular adenosine (eADO) for regulatory and effector T cells (Tregs and Teffs, respectively) has been proposed: inhibiting Teffs and inducing Tregs. The aim of this study was to analyze the action of extracellular nucleotides in human T cells and, moreover, to examine the influence of CD39 and CD73 ectonucleotidases and subsequent adenosine signaling through adenosine 2 receptor (A2 R) in the induction of clinical tolerance after liver transplant. The action of extracellular nucleotides in human T cells was analyzed by in vitro experiments with isolated T cells. Additionally, 17 liver transplant patients were enrolled in an immunosuppression withdrawal trial, and the differences in the CD39-CD73-A2 R axis were compared between tolerant and nontolerant patients. In contrast to the mice, the activation of human Tregs was inhibited similarly to Teffs in the presence of eADO. Moreover, the expression of the enzyme responsible for the degradation of ADO, adenosine deaminase, was higher in tolerant patients with respect to the nontolerant group along the immunosuppression withdrawal. Our data support the idea that eADO signaling and its degradation may play a role in the complex system of regulation of liver transplant tolerance.

Acute Terminal Ileitis in Children: A Retrospective Study in a Pediatric Emergency Department.

OBJECTIVES: This study aims to describe the clinical presentation and outcome of patients diagnosed with acute ileitis in our pediatric emergency department. METHODS: We performed a retrospective study of all patients diagnosed with terminal ileitis by abdominal ultrasonography findings in our pediatric emergency department, over the years 2013 and 2014. Patients with previous diagnosis of inflammatory bowel disease (IBD) were excluded. Data collected were clinical, radiological, and laboratory data at diagnosis; outcome including hospitalization care; and outpatient follow-up in pediatric gastroenterology and/or primary care. RESULTS: A total of 20 cases were retrieved and studied. All of them presented with abdominal pain, 65% located in the right lower quadrant. Leukocyte count, C-reactive protein, and fibrinogen levels (means, 12,889; 4/µL; 50.1 mg/L; and 575 mg/dL, respectively) were above normal range. Hemoglobin and platelet count were normal. A microbial cause of ileitis was found in 3 cases (Yersinia enterocolitica, Campylobacter jejuni, and Adenovirus). Nine patients were referred to a pediatric gastroenterology unit. No cases of IBD were found. CONCLUSIONS: Acute ileitis is a rare and benign cause of abdominal pain in the pediatric emergency department. The main intervention on initial assessment is to rule out potentially severe causes of abdominal pain that could benefit of an emergency surgical procedure. In contrast with adults and adolescents, acute ileitis in children does not have a clear association with development of IBD.

Outbreak of Zika virus pathogenesis and quest of its vaccine development: Where do we stand now?

Zika virus (ZIKV) infection is a life-threatening tropical infection, mainly caused by mosquito bite. After a very long period of quietness, ZIKV infections have become a problematic issue again. Previously, the virus was limited to Africa and Asia only but later it emerged in Brazil, South America, and other parts of the world in 2015. In 2016, there are emerging new cases of sexually transmitted ZIKV infection as well. At present, there is no proper treatment and available pronounced vaccines for the treatment of ZIKV infection. The prime focal point of this review is not only to provide imperative epidemiological information on ZIKV infection in brief but also the current situation of vaccines testing on animal model as well as in clinical trial phases. Currently there is no human vaccine for this pestiferous viral infection. Therefore, prevention, proper management, and up-to-date recommendation are crucial to mitigate the possible risk of vector and non-vector transmission of ZIKV.

Antimicrobial and bactericidal impacts of Bacillus amyloliquefaciens CECT 5940 on fecal shedding of pathogenic bacteria in dairy calves and adult dogs.

Two experiments were carried out to evaluate the bactericidal impacts of Bacillus amyloliquefaciens CECT 5940 on the shedding of faecal pathogenic bacteria in dairy calves (Experiment 1) and in adults dogs (experiment 2). In the calves experiment, a completely randomized design was used to investigate the faecal bacteria profile of Holstein dairy calves fed with either pasteurized waste milk (PWM; n = 9) or a formulated non-medicated milk replacer (NMR; n = 9) for 60 d. The NMR containing sodium-butyrate and the active probiotic B. amyloliquefaciens CECT 5940. In the dogs experiment, addition of same probiotic (i.e., B. amyloliquefaciens CECT 5940) was carried out in two stages. The first stage started from day 7-37, and the second from day 44-71. The assessment of faecal score measured on day 22, 37, 42, 57, 71 and 77 to determine the texture of the stools. Calves received PWM consumed (P < 0.05) more starter feed between day 16 and day 45. The calves fed NMR had more moisture faeces and less cough reflux than the PWM-calves. Feeding NMR to calves increased faecal Klebsiella oxytoca and Proteus vulgaris counts in comparison to PWM-calves. The administration of B. amyloliquefaciens CECT 5940 to the dog diet has no significant effect on the hardness of the stool. Meanwhile, the bacillus count increases while the coliforms count decreases upon B. amyloliquefaciens CECT 5940 administration. This reveals that B. amyloliquefaciens CECT 5940 survived the gastrointestinal passage and rapidly colonized the dog intestine, which could positively affect the metabolism and composition of the intestinal microflora. These results show that B. amyloliquefaciens are a promising probiotic with an antimicrobial and bactericidal activities against the intestinal pathogenic bacteria for dairy calves and adult dogs.

Cardiovascular effects of constant rate infusions of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized at equipotent doses of sevoflurane.

This study evaluated the cardiovascular effects of a constant rate infusion (CRI) of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized with sevoflurane at equipotent doses. Treatments consisted of T1-Lidocaine [loading dose 2 mg/kg body weight (BW), IV, and CRI of 100 µg/kg BW per min] at 1.4% end-tidal of sevoflurane (FESEV); T2-Dexmedetomidine (loading dose 2 µg/kg BW, IV, and CRI of 2 µg/kg BW per hour) and FESEV 1.1%; and T3-Lidocaine-Dexmedetomidine using the same doses of T1 and T2 and FESEV 0.8%. Constant rate infusion of lidocaine did not induce any cardiovascular changes; lidocaine and dexmedetomidine resulted in cardiovascular effects similar to dexmedetomidine alone. These effects were characterized by a significant (P < 0.001) decrease in heart rate, cardiac output, cardiac index, oxygen delivery, and pulmonary vascular resistance index, and a significant (P < 0.001) increase in mean and diastolic arterial pressure, systemic vascular resistance index, pulmonary arterial occlusion pressure and oxygen extraction ratio, compared with baseline values. In conclusion, a CRI of lidocaine combined with dexmedetomidine produces significant cardiovascular changes similar to those observed with dexmedetomidine alone.

Effets cardiovasculaires des infusions constante de taux de lidocaïne, lidocaïne et dexmédétomidine, et dexmédétomidine chez chiens anesthésier at équipotent doses de sevoflurane. L'objet de cette etude a été la evaluation des effets cardo-vasculaires de la perfusion à debit continue (CRI) de lidocaïne, lidocaïene et dexmédétomidine, et dexmédétomidine en chiens anesthésiés avec sévoflurane dans équipotentiel dose. Les traitemets consistèrent á T1-Lidocaïne [dose de charge de 2 mg/kg, IV, et perfusion à debit continue (CRI) de 100 µg/kg/min] en 1,4 % en fin d'expiration du sévoflurane (FESEV); T2-Déxmédetomidine (dose de charge de 2 µg/kg, IV, et perfusion à debit continue (CRI) de 2 µg/kg/h) et FESEV 1,1 % et T3-Lidocaïne-Dexmédétomidine en utilisant la même dose de T1 et T2 et FESEV 0,8 %. Perfusion à debit continue (CRI) de lidocaïne ne induit pas aucun échange cardio-vasculaire; lidocaïne et dexmédétomidine resulta dans effets cardio-vasculaires similaires a dexmédétomidine seule. Ces effets caracterices par significative décroissance (P < 0,001) en fréquence cardiaque, le débit cardiaque, index cardiaque, la libération de l'oxygène, pulmonaire indice de résistance vasculaire, et significative accroissement de la moyenne a la pression artériele diastolique (P < 0,001), indice de résistance vasculaire systémique, et l'extraction d'oxygène. En somme, la perfusion à debit continue (CRI) de lidocaïne produit significative échange cardio-vasculaire similaire à ceux observe en itilisant seulement dexmédétomidine.(Traduit par les auteurs).

Expression and functional roles of Kv7/KCNQ/M-channels in rat medial entorhinal cortex layer II stellate cells.

The medial entorhinal cortex (MEC) is important for spatial navigation and memory. Stellate cells (SCs) of MEC layer II provide major input to the hippocampus, and are thought to be the neuronal correlate of the grid cells. Their electrophysiological properties have been used to explain grid field formation. However, little is known about the functional roles of potassium channels in SCs. M-current is a slowly activating potassium current, active at subthreshold potentials. Although some studies have suggested that Kv7/M-channels may affect subthreshold resonance in SCs, others have found no Kv7/M-current in these cells, so the expression and roles of Kv7/M-channels in SCs are still debated. Using whole-cell voltage-clamp, we have identified a typical M-current with pharmacological properties characteristic of Kv7/M-channels in rat MEC SCs. Current-clamp experiments showed that the specific Kv7/M-channel blocker XE991 increased SCs excitability, and reduced spike frequency adaptation. Our results demonstrate that Kv7/M-channels are expressed in SCs and contribute substantially to regulation of excitability in these cells.

Complementary functions of SK and Kv7/M potassium channels in excitability control and synaptic integration in rat hippocampal dentate granule cells.

The dentate granule cells (DGCs) form the most numerous neuron population of the hippocampal memory system, and its gateway for cortical input. Yet, we have only limited knowledge of the intrinsic membrane properties that shape their responses. Since SK and Kv7/M potassium channels are key mechanisms of neuronal spiking and excitability control, afterhyperpolarizations (AHPs) and synaptic integration, we studied their functions in DGCs. The specific SK channel blockers apamin or scyllatoxin increased spike frequency (excitability), reduced early spike frequency adaptation, fully blocked the medium-duration AHP (mAHP) after a single spike or spike train, and increased postsynaptic EPSP summation after spiking, but had no effect on input resistance (Rinput) or spike threshold. In contrast, blockade of Kv7/M channels by XE991 increased Rinput, lowered the spike threshold, and increased excitability, postsynaptic EPSP summation, and EPSP-spike coupling, but only slightly reduced mAHP after spike trains (and not after single spikes). The SK and Kv7/M channel openers 1-EBIO and retigabine, respectively, had effects opposite to the blockers. Computational modelling reproduced many of these effects. We conclude that SK and Kv7/M channels have complementary roles in DGCs. These mechanisms may be important for the dentate network function, as CA3 neurons can be activated or inhibition recruited depending on DGC firing rate.

Redescription of Brevimulticaecum baylisi () (Nematoda: Heterocheilidae), a parasite of Caiman crocodilus (Crocodylia: Alligatoridae) in the north-eastern Peruvian Amazon.

Caiman crocodilus is among the most abundant and widely distributed predators in the Neotropical region. These animals consume prey such as crustaceans, birds, small mammals, reptiles, amphibians, and fish, which can carry infective larval forms of nematodes. Brevimulticaecum has few studies on its morphology available, lacking detailed images. Therefore, the aim of this study was to redescribe Brevimulticaecum baylisi, stomach parasite of Caiman crocodilus, from subsistence hunting in the Yavari-Mirin River, Peruvian Amazon, using light and scanning electron microscopy. Four caimans were analyzed, and, macroscopically, all had ulcerative lesions in the stomach caused by this parasite. Histopathology showed an inflammatory infiltrate with a predominance of lymphocytes. Morphological characteristics of nematodes include the presence of three diamond-shaped lips wider than they are long, interlabia pyramidal, excretory pore located above the nerve ring, present intestinal cecum, ventriculus with five ventricular appendages, and long, winged spicules. These morphological characters, added to the number and distribution of the pre- and postcloacal papillae of the male specimens, allowed the identification of these parasites as B. baylisi. Scanning electron microscopy of these nematodes showed the presence of a dentigerous ridge on the inner surface of the lips in both sexes, while in males, the presence of a horseshoe-shaped median papilla was observed on the upper lip of the cloaca. Our research, therefore, adds these characteristics to the original description of B. baylisi, in addition to expanding the biogeographical distribution of this parasite.

Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine.

The impacts of morphine and dexmedetomidine on the MAC of isoflurane were studied in rats constantly medicated with the cannabinoid WIN 55,212-2. METHODS: Prior to the administration of morphine, the MAC was measured in both untreated rats (MAC (ISO)) and those treated with a cannabinoid (MAC (ISO + CANN)). The effects of morphine (MAC (ISO + MOR)) and dexmedetomidine (MAC (ISO + DEX)) on untreated rats and rats treated for 21 days with the cannabinoids (MAC (ISO + CANN + MOR)) and (MAC (ISO + CANN + DEX) were also studied. RESULTS: MAC (ISO) was 1.32 ± 0.06, and MAC (ISO + CANN) was 1.69 ± 0.09. MAC (ISO + MOR) was 0.97 ± 0.02 (26% less than MAC (ISO)). MAC (ISO + CANN + MOR) was 1.55 ± 0.08 (8% less than MAC (ISO + CANN)), MAC (ISO + DEX) was 0.68 ± 0.10 (48% less than MAC (ISO)), and MAC (ISO + CANN + DEX) was 0.67 ± 0.08 (60% less than MAC (ISO + CANN)). CONCLUSIONS: Medication with a cannabinoid for 21 days augmented the MAC of isoflurane. The sparing effect of morphine on isoflurane is lower in rats constantly medicated with a cannabinoid. The sparing effect of dexmedetomidine on the minimum alveolar concentration of isoflurane is greater in rats repeatedly medicated with a cannabinoid.

Therapeutic strategies and clinical evolution of patients with infantile fibrosarcoma: a unique paediatric case series.

BACKGROUND: Infantile fibrosarcoma is the most frequent soft tissue sarcoma in newborns or children under one year of age. This tumour often implies high local aggressiveness and surgical morbidity. The large majority of these patients carry the ETV6-NTRK3 oncogenic fusion. Hence, the TRK inhibitor larotrectinib emerged as an efficacious and safe alternative to chemotherapy for NTRK fusion-positive and metastatic or unresectable tumours. However, real-world evidence is still required for updating soft-tissue sarcoma practice guidelines. OBJECTIVE: To report our experience with the use of larotrectinib in pediatric patients. METHODS: Our case series shows the clinical evolution of 8 patients with infantile fibrosarcoma under different treatments. All patients enrolled in this study received informed consent for any treatment. RESULTS: Three patients received larotrectinib in first line. No surgery was needed with larotrectinib, which led to the rapid and safe remission of tumours, even in unusual anatomical locations. No significant adverse effects were observed with larotrectinib. CONCLUSION: Our case series supports that larotrectinib may be a therapeutic option for newborn and infant patients with infantile fibrosarcoma, especially in uncommon locations.

Effects of Microencapsulated Essential Oils on Equine Health: Nutrition, Metabolism and Methane Emission.

This review examines the available data regarding the positive effects of microencapsulated essential oils (EOs) on the nutrition, metabolism, and possibly the methane emission of horses. A literature review was conducted on the effect of microencapsulated (EOs) on the health of horses. The information comprises articles published in recent years in indexed journals. The results indicate that mixtures of microencapsulated EOs may be beneficial to equine health due to their antimicrobial and antioxidant activity, as well as their effects on enteric methane production, nutrient absorption, and immune system enhancement. Moreover, encapsulation stabilizes substances such as EOs in small doses, primarily by combining them with other ingredients.

Chaperone-Mediated Autophagy Ablation in Pericytes Reveals New Glioblastoma Prognostic Markers and Efficient Treatment Against Tumor Progression.

Background: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet. Thus, we proposed to analyze the contribution of CMA to other GB-induced changes in PC biology and determine if CMA ablation in PC is a key target mechanism for GB treatment. Methods: Studies of RNA-seq and secretome analysis were done in GB-conditioned PC with and without CMA (from knockout mice for LAMP-2A) and compared to control PC. Different therapeutic strategies in a GB mouse model were compared. Results: We found several gene expression pathways enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Phagosome formation, cellular senescence, focal adhesion and the effector function to promote anti-tumor immune responses were the most affected pathways, revealing a transcriptomic profiling of specific target functions useful for future therapies. In addition, several molecules associated with tumor mechanisms and related to tumor immune responses such as gelsolin, periostin, osteopontin, lumican and vitamin D, were identified in the PC secretome dependent on GB-induced CMA. The CMA ablation in PC with GB cells showed an expected immunogenic phenotype able to phagocyte GB cells and a key strategy to develop future therapeutic strategies against GB tumor progression. A novel intravenous therapy using exofucosylated CMA-deficient PC was efficient to make PC reach the tumor niche and facilitate tumor elimination. Conclusion: Our results corroborate previous findings on the impaired immunogenic function of PC with GB-induced CMA, driving to other altered PC functions and the identifications of new target markers related to the tumor immune responses and useful for GB prognosis/therapy. Our work demonstrates CMA ablation in PC as a key target mechanism to develop a successful therapy against GB progression.

Minimum Alveolar Concentration of Isoflurane in Rats Chronically Treated with the Synthetic Cannabinoid WIN 55,212-2.

The minimum alveolar concentration MAC of isoflurane was measured in rats chronically treated with WIN 55,212-2. METHODS: The MAC of isoflurane was determined in 24 male rats from expiratory samples at time of tail clamping under the following conditions: without treatment MAC(ISO), in rats treated for 21 days with WIN 55,212-2 MAC(ISO + WIN55), and in rats 8 days after stopping treatment with WIN 55,212-2 (MACISO + WIN55 + 8D). RESULTS: The MAC(ISO) was 1.32 ± 0.06. In the MAC(ISO + WIN55) group, the MAC increased to 1.69 ± 0.09 (28%, p-value ≤ (0.0001). Eight days after stopping treatment with WIN55, the MAC did not decrease significantly, 1.67 ± 0.07 (26%, p-value ≤ 0.0001). CONCLUSIONS: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. This effect does not disappear 8 days after discontinuation of treatment with the synthetic cannabinoid.