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In order to know whether there is a risk of anisakiasis (or anisakidosis) by consumption of fish of the genus Mullus from the western Mediterranean Sea, which are appreciated for their quality, an epidemiological survey was carried out to evaluate the occurrence of zoonotic or potentially zoonotic nematodes in M. barbatus and M. surmuletus. Although the presence of the third larval stage (L3) of anisakids (Anisakis and Contracaecum) has been previously described in these fish, the results showed the absence of anisakids and the presence, never in muscle, of L3 and L4 of raphidascaridids of the genus Hysterothylacium, molecularly identified as H. fabri. Phylogenetic analysis groups them into the Mediterranean Sea clade, far from individuals isolated in the Pacific Ocean. Prevalence was slightly higher, but not significant, in M. barbatus versus M. surmuletus (72.3% vs 60.0%), but mean intensity (MI) and mean abundance (MA) parameters were approximately twice as high in M. barbatus as in M. surmuletus (MI 5.8 vs 2.8, p = .001; MA 4.2 vs 1.7, p < .001). The presence of the parasite seems to have different effects on these two sympatric species. In M. barbatus it seems to affect their growth, as it appreciably reduces the value of allometry coefficient in infected fish (2.78 vs. 2.18). On the other hand, in M. surmuletus the infection significantly (p < .04) affects the Fulton's condition factor, an indicator of the health status of the fish. It can be concluded that the ingestion of these fish by the people poses negligible risk of anisakiasis, but the consumer should continue to be urged to follow the rules of prevention against this illness., (© 2024 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Objectives: Cannabidiol (CBD) is a phytocannabinoid with great potential in clinical applications. The mechanism(s) of action of CBD require further investigation. Previous studies suggested that adenosine A 2A receptors (A 2A Rs) could play a role in CBD-induced effects. Here, we evaluated the ability of CBD to modify the function of A 2A R., Methods: We used HEK-293T cells transfected with the cDNA encoding the human A 2A R and Gαs protein, both modified to perform bioluminescence-based assays. We first assessed the effect of CBD on A 2A R ligand binding using an A 2A R NanoLuciferase sensor. Next, we evaluated whether CBD modified A 2A R coupling to mini-Gαs proteins using the NanoBiT™ assay. Finally, we further assessed CBD effects on A 2A R intrinsic activity by recording agonist-induced cAMP accumulation., Results: CBD did not bind orthosterically to A 2A R but reduced the coupling of A 2A R to Gαs protein and the subsequent generation of cAMP., Conclusion: CBD negatively modulates A 2A R functioning.

A combination of Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD) at non-psychoactive doses was previously demonstrated to reduce cognitive decline in APP/PS1 mice, an animal model of Alzheimer's disease (AD). However, the neurobiological substrates underlying these therapeutic properties of Δ 9 -THC and CBD are not fully understood. Considering that dysregulation of glutamatergic activity contributes to cognitive impairment in AD, the present study evaluates the hypothesis that the combination of these two natural cannabinoids might reverse the alterations in glutamate dynamics within the hippocampus of this animal model of AD. Interestingly, our findings reveal that chronic treatment with Δ 9 -THC and CBD, but not with any of them alone, reduces extracellular glutamate levels and the basal excitability of the hippocampus in APP/PS1 mice. These effects are not related to significant changes in the function and structure of glutamate synapses, as no relevant changes in synaptic plasticity, glutamate signaling or in the levels of key components of these synapses were observed in cannabinoid-treated mice. Our data instead indicate that these cannabinoid effects are associated with the control of glutamate uptake and/or to the regulation of the hippocampal network. Taken together, these results support the potential therapeutic properties of combining these natural cannabinoids against the excitotoxicity that occurs in AD brains., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ester Aso reports financial support was provided by Spain Ministry of Science and Innovation. Jordi Bonaventura reports financial support was provided by Spain Ministry of Science and Innovation. Francisco Ciruela reports financial support was provided by Spain Ministry of Science and Innovation. Xavier Gasull reports financial support was provided by Spain Ministry of Science and Innovation. Francisco Ciruela reports financial support was provided by Departament de Recerca i Universitats de la Generalitat de Catalunya. Ester Aso reports financial support was provided by CYTED-Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The cannabinoid system is one of the most investigated neuromodulatory systems because of its involvement in multiple pathologies such as cancer, inflammation, and psychiatric diseases. Recently, the CB2 receptor has gained increased attention considering its crucial role in modulating neuroinflammation in several pathological conditions like neurodegenerative diseases. Here we describe the rational design of pyrrole-based analogues, which led to a potent and pharmacokinetically suitable CB2 full agonist particularly effective in improving cognitive functions in a scopolamine-induced amnesia murine model. Therefore, we extended our study by investigating the interconnection between CB2 activation and neurotransmission in this experimental paradigm. To this purpose, we performed a MALDI imaging analysis on mice brains, observing that the administration of our lead compound was able to revert the effect of scopolamine on different neurotransmitter tones, such as acetylcholine, serotonin, and GABA, shedding light on important networks not fully explored, so far., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Carnitine palmitoyltransferase 1c (CPT1C) is a neuron-specific protein widely distributed throughout the CNS and highly expressed in discrete brain areas including the hypothalamus, hippocampus, amygdala and different motor regions. Its deficiency has recently been shown to disrupt dendritic spine maturation and AMPA receptor synthesis and trafficking in the hippocampus, but its contribution to synaptic plasticity and cognitive learning and memory processes remains mostly unknown. Here, we aimed to explore the molecular, synaptic, neural network and behavioural role of CPT1C in cognition-related functions by using CPT1C knockout (KO) mice. CPT1C-deficient mice showed extensive learning and memory deficits. The CPT1C KO animals exhibited impaired motor and instrumental learning that seemed to be related, in part, to locomotor deficits and muscle weakness but not to mood alterations. In addition, CPT1C KO mice showed detrimental hippocampus-dependent spatial and habituation memory, most probably attributable to inefficient dendritic spine maturation, impairments in long-term plasticity at the CA3-CA1 synapse and aberrant cortical oscillatory activity. In conclusion, our results reveal that CPT1C is not only crucial for motor function, coordination and energy homeostasis, but also has a crucial role in the maintenance of learning and memory cognitive functions. KEY POINTS: CPT1C, a neuron-specific interactor protein involved in AMPA receptor synthesis and trafficking, was found to be highly expressed in the hippocampus, amygdala and various motor regions. CPT1C-deficient animals exhibited energy deficits and impaired locomotion, but no mood changes were found. CPT1C deficiency disrupts hippocampal dendritic spine maturation and long-term synaptic plasticity and reduces cortical γ oscillations. CPT1C was found to be crucial for motor, associative and non-associative learning and memory., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objectives: To compare between 2 sedoanalgesia regimes, the time from withdrawal of the medication until the patient wakes up and until extubation., Methodology: Observational study on pediatric patients after elective surgery that needed mechanical ventilation for a period maximum to 72 h. We compared two independent groups of patients: group A: patients collected prospectively who received sedoanalgesia with propofof-remifentanil and group B: patients who received midazolam-fentanyl collected retrospectively by reviewing medical records and database of the unit. The main variables studied were: Age, weight, sex, interventions type, sedoanalgesia scales, drugs dosages, time from withdrawal of medication to awakening and extubation, and adverse effects., Results: We collected 82 patients, 43 in group A and 39 in group B. Age (arithmetical mean ± standard deviation of patients were 49 ± 65 months, weight 17 ± 16 kg. Mechanical ventilation medium time was 22 h (3-72), wake-up time from withdrawal after removing sedoanalgesia was of 11,8 ± 10,6 min group A and 137,3 ± 45 min group B (P < 0.001), extubation time after removing sedoanalgesia was of 24 ± 21 min group A and 230 ± 102 min group B (P < 0.001). Adverse effects were found in 10.5% of patients group A (7.9% agitation, 2.6% bradycardia), and 13% of patients group B (respiratrory depression after extubation) P = 0,572., Conclusions: Patients treated with propofol-remifentanil have significantly shorter times to wake up, extubation and withdrawal from mechanical ventilation after stopping the medication. In the midazolam-fentanyl group, respiratory depression was more frequent, although the percentage of adverse effects were similar in both groups. Both the combination of propofol-remifentanil and midazolam-fentanyl appear to be effective as a sedative-analgesic regimen for patients undergoing mechanical ventilation after surgery., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: RTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death in in vitro and in vivo models of Parkinson's and Huntington's diseases and is up regulated in compromised neurons in human postmortem brains of both neurodegenerative disorders. Indeed, in both Parkinson's and Huntington's disease mouse models, RTP801 knockdown alleviates motor-learning deficits., Results: We investigated the physiological role of RTP801 in neuronal plasticity and we found RTP801 in rat, mouse and human synapses. The absence of RTP801 enhanced excitatory synaptic transmission in both neuronal cultures and brain slices from RTP801 knock-out (KO) mice. Indeed, RTP801 KO mice showed improved motor learning, which correlated with lower spine density but increased basal filopodia and mushroom spines in the motor cortex layer V. This paralleled with higher levels of synaptosomal GluA1 and TrkB receptors in homogenates derived from KO mice motor cortex, proteins that are associated with synaptic strengthening., Conclusions: Altogether, these results indicate that RTP801 has an important role modulating neuronal plasticity and motor learning. They will help to understand its role in neurodegenerative disorders where RTP801 levels are detrimentally upregulated., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Compare between 2sedoanalgesia regimes, the time from withdrawal of the medication until the patient wakes up and until extubation., Methodology: Observational study on pediatric patients after elective surgery that needed mechanical ventilation for a period maximum to 72hours. We compared 2independent groups of patients: group A: patients collected prospectively who received sedoanalgesia with propofof-remifentanil and group B: patients who received midazolam-fentanyl collected retrospectively by reviewing medical records and database of the unit. The main variables studied were: Age, weight, sex, interventions type, sedoanalgesia scales, drugs dosages, time from withdrawal of medication to awakening and extubation, and adverse effects., Results: We collected 82 patients, 43 in group A and 39 in group B. Age (arithmetical mean±standard deviation of patients were 49±65 months, weight 17±16kg. Mechanical ventilation time medium was 22hours (3-72), wake-up time from withdrawal after removing sedoanalgesia was of 11,8±10,6minutes group A and 137,3±45minutes group B (P<.001), extubation time after removing sedoanalgesia was of 24±21minutes group A and 230±102minutes group B (P<.001). Adverse effects were found in 10.5% of patients group A (7.9% agitation, 2.6% bradycardia), and 13% of patients group B (respiratrory depression after extubation), P=.572., Conclusions: Patients treated with propofol-remifentanil have significantly shorter times to wake up, extubation and withdrawal from mechanical ventilation after stopping the medication. In the midazolam-fentanyl group, respiratory depression was more frequent, although the percentage of adverse effects were similar in both groups. Both the combination of propofol-remifentanil and midazolam-fentanyl appear to be effective as a sedative-analgesic regimen for patients undergoing mechanical ventilation after surgery., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

AMPARs control fast synaptic communication between neurons and their function relies on auxiliary subunits, which importantly modulate channel properties. Although it has been suggested that AMPARs can bind to TARPs with variable stoichiometry, little is known about the effect that this stoichiometry exerts on certain AMPAR properties. Here we have found that AMPARs show a clear stoichiometry-dependent modulation by the prototypical TARP γ2 although the receptor still needs to be fully saturated with γ2 to show some typical TARP-induced characteristics (i.e. an increase in channel conductance). We also uncovered important differences in the stoichiometric modulation between calcium-permeable and calcium-impermeable AMPARs. Moreover, in heteromeric AMPARs, γ2 positioning in the complex is important to exert certain TARP-dependent features. Finally, by comparing data from recombinant receptors with endogenous AMPAR currents from mouse cerebellar granule cells, we have determined a likely presence of two γ2 molecules at somatic receptors in this cell type., Competing Interests: FM, NS, NY, XG, EG, DS No competing interests declared, (© 2020, Miguez-Cabello et al.)

In neurons, AMPA receptor (AMPAR) function depends essentially on their constituent components:the ion channel forming subunits and ion channel associated proteins. On the other hand, AMPAR trafficking is tightly regulated by a vast number of intracellular neuronal proteins that bind to AMPAR subunits. It has been recently shown that the interaction between the GluA1 subunit of AMPARs and carnitine palmitoyltransferase 1C (CPT1C), a novel protein partner of AMPARs, is important in modulating surface expression of these ionotropic glutamate receptors. Indeed, synaptic transmission in CPT1C knockout (KO) mice is diminished supporting a positive trafficking role for that protein. However, the molecular mechanisms of such modulation remain unknown although a putative role of CPT1C in depalmitoylating GluA1 has been hypothesized. Here, we explore that possibility and show that CPT1C effect on AMPARs is likely due to changes in the palmitoylation state of GluA1. Based on in silico analysis, Ser 252, His 470 and Asp 474 are predicted to be the catalytic triad responsible for CPT1C palmitoyl thioesterase (PTE) activity. When these residues are mutated or when PTE activity is inhibited, the CPT1C effect on AMPAR trafficking is abolished, validating the CPT1C catalytic triad as being responsible for PTE activity on AMPAR. Moreover, the histidine residue (His 470) of CPT1C is crucial for the increase in GluA1 surface expression in neurons and the H470A mutation impairs the depalmitoylating catalytic activity of CPT1C. Finally, we show that CPT1C effect seems to be specific for this CPT1 isoform and it takes place solely at endoplasmic reticulum (ER). This work adds another facet to the impressive degree of molecular mechanisms regulating AMPAR physiology.

Objective: To determine the prevalence of tuberculosis infection and annual risk of infection in the school population of Ceuta., Method: A cross-sectional study was conducted. A tuberculin test (2UT RT-23 Tween 80) was given to 7-year-old schoolchildren in Ceuta in 2008. A positive result was considered as an induration of ≥5 mm at 72 hours in unvaccinated children., Results: A total of 612 children were studied. The prevalence of tuberculosis infection was 0.98% (95% confidence interval with a 2.5% margin of error). The distribution showed differences among three health areas, and was greatest in the most deprived area (2.07%). The annual risk of infection was 0.15%., Conclusions: According to the most recent studies, the prevalence of tuberculosis infection in Ceuta is one of the highest of Spain. Our results do not agree with the epidemiological data for tuberculosis in Ceuta, which also includes imported cases., (Copyright © 2011 SESPAS. Published by Elsevier España. All rights reserved.)

Background: Bile duct injuries (BDI) have a wide array of presentation. Left partial injuries (Strasberg D) of the hepatic duct are the result of excessive traction, which dissects the hepatic hilum and provokes medial perforations without continuity loss. Right partial injuries (Strasberg A, B and C) are produced by direct damage to the hepatic duct or isolated injury to the right and accessory ducts. It is important to determine frequency, spectrum and treatment outcome of this BDI in the surgical scenario., Methods: Patients with BDI who underwent surgical treatment in our hospital were reviewed, right and left partial injuries were selected. Demographic, clinical and therapeutic data were analyzed., Results: In a 16-year period, 405 patients underwent surgical treatment of BDI. 31 (8%) were classified as a left partial injury (Strasberg D): 23 injuries at the common hepatic duct treated with a Hepatojejunostomy (HJ); four at the confluence level which received a HJ with neoconfluence construction; two partial injuries in the left hepatic duct underwent a selective left HJ; and two complete occlusions of the left hepatic duct, one treated with a partial hepatectomy and the last case underwent a partial HJ. Right partial injuries (Strasberg A, B or C) were identified in 21 cases (5%), their treatment was tailored according to the type of BDI (conservative, selective HJ, or hepatectomy)., Conclusions: In our series the frequency of left and right partial BDI injuries was 8% and 5%, respectively. The spectrum of analyzed injuries included four subtypes for the left partial and eight for the right partial lesions. Most BDI in the two analyzed groups presented concomitant devascularization of the extra-hepatic ducts, therefore receiving surgical treatment rather than endoscopic treatment was done.

Despite the screening efforts in the general population and particularly in families with hereditary colon cancer, locally advanced colon cancer remains a common clinical problem. In block resection is considered mainstay therapy in these patients. The aim of this report is to present a case of right-sided colon cancer with a medullar phenotype invading the duodenum treated through in block resection. A case of a 54-year-old male with a family history of colon and pancreatic cancer with lower gastrointestinal tract bleeding is presented. Colonoscopy and computed tomography scan showed a tumor in the colonic hepatic flexure invading the duodenum. The patient underwent an in block resection of the right colon, duodenum, pancreas and antrum. The histopathological study showed a T4N0M0 adenocarcinoma invading the duodenum, pancreas and antrum with negative margins. His postoperative evolution was complicated with a pancreatic fistula, which resolved with conservative measures. In conclusion, in block resection is the treatment of choice for locally advanced colon cancer with invasion to duodenum and pancreas and should be performed in high-volume centers familiar with this type of procedures. Key words: pancreaticoduodenectomy, colon cancer, Lynch syndrome, pancreas, surgery, Mexico.

Objective: Our aim was to analyse clinical, diagnostic, therapeutical and evolutionary features in a pediatric population with tuberculous meningitis., Patients and Methods: The medical records of thirteen children with this diagnosis admitted to Hospital Infantil Virgen del Rocío from Seville (Spain) between 1984 and 1999 were reviewed., Results: The mean age was 2,35 +/- 2,3 years. The symptoms upon admission were: fever in 11 children, anorexia and vomiting in 8, disturbance of the consciousness in 7. Meningeal signs in 6, all of them older than 20 months, the remaining seven showed irritability and four of these ones hypertense fontanelles. Three patients were in the first stage of the disease, 9 in the second and 1 in the third, according to the Medical Research Council. CSF findings were indicative in all the cases. Five children had bacilloscopy positive and Mycobacterium tuberculosis was isolated in 6 patients, sometimes in CSF others in gastric juice. Mantoux skin test was positive in 11. Radiographic studies demonstrated abnormal chest findings in 8 patients (hiliar adenopathy, 1; miliary pattern, 2; and infiltrates, 5). Pathology cranial computed tomography showed in all the cases and the electroencephalogram was slowed down in the initial phases in 11. Two children died and the neurological complications were the most frequent, appearing in 9 patients. Without consequences cured 4 patients, the rest presented cognitive, visual and motor deficits, sensibility skin disturbance and late seizures. No case has been observed during the last 5 years., Conclusions: Fast diagnosis tests used for M. tuberculosis identification were useful to begin an antituberculous treatment in a high suspicion of meningeal affectation by this German patient. The early treatment will decrease complications and consequences by this disease. A decrease in the incidence looks to be in spite of the VIH infection increase nowadays.