Immediate Implant Placement in the Aesthetic Area using Inverted Body-shift Design: A Prospective Clinical Pilot Study.

A prospective clinical pilot study was carried out to evaluate a novel macroimplant design with a 12° angled platform. The implant is placed at the center of the socket, optimizing all the alveolar bone. In addition, the prosthetic emergence should be ideal, as it is corrected and emerges through the cingulate area. Twelve patients were enrolled in an immediate implant placement procedure with immediate aesthetic rehabilitation to replace an anterior maxillary tooth, and were treated with inverted body-shift design with 12° angled neck. Only type I sockets according to the Elian classification were considered eligible for the study. There were no implant failures after one year of loading. Regarding the horizontal and vertical hard tissue changes, there was a statistically significant median overall horizontal change of -0.99 mm at 1 mm and of -0.61 mm at 3 mm. On the other hand, stability was observed at 5 mm, since the result obtained was not statistically significant. The median pink esthetic score (PES) at one year of follow-up was 11.5. This implant may be useful in the immediate tooth replacement treatment of maxillary anterior post-extraction sockets, nevertheless, comparative studies with conventional implants should be carried out.

Bi-phasic regulation of miR-17~92 transcription during hypoxia: Roles of HIF1 and p53 hyperphosphorylation at ser15.

We have reported previously that during hypoxia exposure, the expression of mature miR-17~92 was first upregulated and then downregulated in pulmonary artery smooth muscle cells (PASMC) and in mouse lungs in vitro and in vivo. Here we investigated the mechanisms regulating this bi-phasic expression of miR-17~92 in PASMC in hypoxia. We measured the level of primary miR-17~92 in PASMC during hypoxia exposure and found that short-term hypoxia exposure (3%O2, 6 hours) induced the level of primary miR-17~92, while long-term hypoxia exposure (3%O2, 24 hours) decreased its level, suggesting a bi-phasic regulation of miR-17~92 expression at the transcriptional level. We found that short-term hypoxia-induced upregulation of miR-17~92 was HIF1α and E2F1 dependent. Two HIF1α binding sites on miR-17~92 promoter were identified. We also found that long-term hypoxia-induced suppression of miR-17~92 expression could be restored by silencing of p53. Mutation of the p53-binding sites in the miR-17~92 promoter increased miR-17~92 promoter activity in both normoxia and hypoxia. Our findings suggest that the bi-phasic transcriptional regulation of miR-17~92 during hypoxia is controlled by HIF1/E2F1 and p53 in PASMC: during short-term hypoxia exposure, stabilization of HIF1 and induction of E2F1 induces the transcription of miR-17~92; while during long-term hypoxia exposure, hyperphosphorylation of p53 suppresses the expression of miR-17~92.

The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that continuous positive airway pressure (CPAP) could have a favorable impact on these complications. We assessed the feasibility of conducting a randomized control trial in patients with type 2 diabetes and OSA over 2 years. METHODS: We conducted an open-label multicenter feasibility randomized control trial of CPAP vs no CPAP in patients with type 2 diabetes and OSA. Patients with resting oxygen saturation < 90%, central apnea index > 15 events/h, or Epworth Sleepiness Scale ≥ 11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomly assigned, with a median (interquartile range) follow-up of 645 (545, 861) days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomly assigned to CPAP and several diabetes-related end points (chronic kidney disease, neuropathy, and quality of life). CONCLUSIONS: It was feasible to recruit, randomly assign, and achieve a high follow-up rate over 2 years in patients with OSA and type 2 diabetes. CPAP compliance might improve by a run-in period before randomization. A full randomized control trial is necessary to assess the observed favorable association between CPAP and chronic kidney disease , neuropathy, and quality of life in patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; Name: The impact of sleep disorders in patients with type 2 diabetes; URL: https://www.isrctn.com/ISRCTN12361838; Identifier: ISRCTN12361838. CITATION: Makhdom EA, Maher A, Ottridge R, et al. The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial. J Clin Sleep Med. 2024;20(6):947-957.

Muscle Hypertrophy Is Linked to Changes in the Oxidative and Proteolytic Systems during Early Tenderization of the Spanish Breed "Asturiana de los Valles".

For fresh meat consumers, eating satisfaction is of utmost importance and tenderness is one of the most important characteristics in this regard. Our study examined beef of different animal biotypes of the autochthonous breed "Asturiana de los Valles" (AV) to determine if early postmortem oxidative and proteolytic processes may influence the final tenderness of the product. This meat-specialized breed shows different biotypes depending on the frequency of a myostatin mutation "mh" that induces double-muscling or muscular hypertrophy (mh/mh, mh/+, +/+). Samples from the longissimus dorsi muscles of yearling bulls were analyzed during the first 24 h postmortem. Changes in the redox balance of muscle cells were significant in the first hours after slaughter; total antioxidant activity was higher in the mh/mh biotype and it followed the shortening of the sarcomeres, a key parameter in understanding meat tenderness. The two proteolytic systems studied (proteasome and lysosome) followed distinct patterns. Proteasome activity was higher in the (mh/+) biotype, which correlated with higher protein damage. Lysosome proteolysis was increased in the more tender biotypes (mh genotypes). Autophagic activation showed significant differences between the biotypes, with (mh/mh) showing more intense basal autophagy at the beginning of the postmortem period that decreased gradually (p < 0.001), while in the normal biotype (+/+), it was slightly delayed and then increased progressively (p < 0.001). These results suggest that this type of catalytic process and antioxidant activity could contribute to the earlier disintegration of the myofibers, particularly in the mh/mh biotypes, and influence the conversion of muscle into meat.

Molecular formula assignment of dissolved organic matter by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry using two non-targeted data processing approaches: A case study from recirculating aquaculture systems.

BACKGROUND: The accumulation of dissolved organic matter (DOM) poses an issue in the management of the water quality from recirculating aquaculture systems (RAS), but its characterization is often not detailed enough to understand the DOM transformations in RAS. In this study, we investigated the application of two distinct non-targeted data processing approaches using ultra-performance liquid chromatography (UPLC) with quadrupole time-of-flight mass spectrometry (QTOF-MS) and two software with different algorithmic designs: PetroOrg and Progenesis QI to accurately characterize the molecular composition of DOM in RAS by UPLC-QTOF-MS. RESULTS: The UPLC-QTOF-MS resolution in combination with PetroOrg and Progenesis QI software successfully assigned 912 and 106 unique elemental compositions, respectively, including compounds containing carbon, hydrogen, and oxygen (CHO) and nitrogen-containing CHO compounds (CHON), in the DOM samples from RAS. The results of these two distinct data processing approaches were consistent with the list of DOM formulas from RAS identified by higher resolution mass spectrometry techniques confirming their reliability. PetroOrg approach revealed only compositional information in the DOM samples from RAS, while Progenesis QI in addition to identifying new elemental compositions, increased their chemical space by giving information about their polarity and their possible key structures. DOM samples from RAS were found to be rich in unsaturated CHO compounds, with tentatively key structures of terpenoids with medium polarity indicating natural origins in their composition. The analysis also revealed probable structures of sucrose fatty acid esters and polyethylene glycol, indicating anthropogenic sources. SIGNIFICANCE AND NOVELTY: The combination of these two non-targeted data processing approaches significantly improves the characterization of the complex mixture of DOM from RAS by UPLC-QTOF-MS reporting for the first time accurate DOM results in terms of its composition, while proposing its key structures. The presented methods can also be used to analyze different DOM samples with other HRMS techniques and software.

A probable case of an "Hourglass" epidermoid cyst located in the posterior fossa in an individual from Ibi, Alicante, Spain (12th-13th centuries AD).

Epidermoid bone cysts are rare, unilocular, and slow growing. They develop by the accumulation of ectodermal remnants, and they may be congenital or acquired. The most common locations for these bone cysts are the distal phalanges, followed by the skull. This paper documents an adult male from the Islamic (twelfth and thirteen centuries CE) burial site of Ibi in the Province of Alicante, southeast Spain. This individual had a cranial lesion in the form of a roughly elliptical hole in the posterior fossa (left occipital region). The lesion was examined macroscopically and using X-ray photography. Based on the shape of the lesion, the most likely diagnosis would appear to be a benign tumour, a so-called "hourglass" epidermoid cyst. No direct link between this tumour and the cause of death can be established.

Comparative study of the efficacy and safety of Abexol (suspension versus tablets) in patients with gastrointestinal symptoms.

BACKGROUND/AIMS: Abexol is a mixture of primary aliphatic alcohols purified from beeswax (Apis mellifera), that produces anti-inflammatory, antioxidant and gastroprotective effects, as well as it is safe and well tolerated. To investigate and compare the efficacy and safety of Abexol (suspension versus tablets) in patients with gastrointestinal symptoms. METHODS: Monocentric study, open-label, randomized design, with two parallel groups receiving Abexol tablets (150 mg/d) or Abexol suspension (75 mg/d) for 8 weeks. Primary efficacy variable (significant improvement in the total score of Gastrointestinal Symptom Rating Scale [GSRS]). Significant reduction in the intensity of the gastrointestinal-symptoms and the reduction in the consumption of antacids are considered secondary efficacy variable. Short form-36 (SF-36) quality of life questiongenonaire was evaluated as collateral variable. Data were analyzed as per intention to treat. RESULTS: A significantly decrease in the overall score of the survey was observed with respect to the baseline level (p < 0.001) of 81.4% in the Abexol suspension group and 77.9% in the Abexol tablets group. At the end of the trial, most gastrointestinal- symptoms disappeared or reduced significantly. The frequency of consumption of neutralizing antacids was low. The significantly improvement in the perception of the state of health obtained in the Abexol is in correspondence with the improvement achieved in some of the components evaluate in the SF-36 questionnaire. Both treatments were safe and well tolerated. CONCLUSION: Abexol suspension showed efficacy and safety similar to Abexol tablets in patients with gastrointestinal symptoms, but using half the dose.

Widespread synchronous decline of Mediterranean-type forest driven by accelerated aridity.

Large-scale, abrupt ecosystem change in direct response to climate extremes is a critical but poorly documented phenomenon1. Yet, recent increases in climate-induced tree mortality raise concern that some forest ecosystems are on the brink of collapse across wide environmental gradients2,3. Here we assessed climatic and productivity trends across the world's five Mediterranean forest ecosystems from 2000 to 2021 and detected a large-scale, abrupt forest browning and productivity decline in Chile (>90% of the forest in <100 days), responding to a sustained, acute drought. The extreme dry and warm conditions in Chile, unprecedented in the recent history of all Mediterranean-type ecosystems, are akin to those projected to arise in the second half of the century4. Long-term recovery of this forest is uncertain given an ongoing decline in regional water balance. This dramatic plummet of forest productivity may be a spyglass to the future for other Mediterranean ecosystems.

Assessing the Taxonomic Status of the Gray Brocket Mazama simplicicornis argentina Lönnberg, 1919 (Artiodactyla: Cervidae).

Mazama simplicicornis argentina is the name that was given to describe a gray brocket collected by Lönberg in 1919 in the central Chaco region of Argentina. Subsequent authors, based on morphological similarities, considered this name to be a synonym for the species Subulo gouazoubira Fischer, 1814 from Paraguay. In the absence of genetic analyses to compare the Argentinian and Paraguayan gray brockets, we aimed to clarify the taxonomy of M. simplicicornis argentina through an integrative assessment using morphological, cytogenetical, and molecular data from its holotype and a current topotype. Qualitative skull features and cranio-morphometric results of M. simplicicornis argentina showed a great similarity with the S. gouazoubira neotype characters. The diploid chromosome number of M. simplicicornis argentina topotype corresponded with the karyotypical pattern of S. gouazoubira with 2n = 70 and FN = 70, showing a great similarity in all classic and molecular cytogenetic results and revealing the homologies between karyotypes. The phylogenetic analysis of mitochondrial genes used in this study (concatenated partial ND5 and Cytb gene) allocated the M. simplicicornis argentina specimens in the monophyletic clade of S. gouazoubira with a branch value of 100%. These results show that there is no discontinuity between the Argentinian and Paraguayan gray brockets. Therefore, the individuals originally described as M. simplicicornis argentina should be recognized as S. gouazoubira.

Per- and poly-fluoroalkyl substances in Tawny Owl (Strix aluco) feathers from Trøndelag, Norway.

Per- and polyfluoroalkyl substances (PFASs) are contaminants of global concern due to their ubiquitous occurrence in the environment, bioaccumulation and the adverse effects on organisms. Tawny Owls (Strix aluco) are documented to be exposed to increasing concentrations of perfluoroalkyl carboxylic acids (PFCAs), and have been suggested in literature as a key raptor monitoring species. Therefore, non-destructive biomonitoring efforts are of high interest. Thus far, the use of feathers for biomonitoring PFASs in Tawny Owls has not been investigated. In this study, 32 PFASs were analyzed in 49 Tawny Owl body feather samples collected from 2017 to 2020 in Trøndelag, Norway. There were 30 PFASs detected in at least one feather, with the sum concentrations ranging from 31 to 203 ng/g (w.w.). Perfluoroheptanoic acid (PFHpA) (median: 33 ng/g) and perfluorooctane sulfonamidoacetic acid (FOSAA) (median: 18 ng/g) were the two compounds with the highest concentrations. Perfluorooctane sulfonic acid (PFOS), which is banned for production and use in Norway since 2007, was found in all samples (median: 4.14 ng/g), indicating its high persistence. 8 PFASs were detected in at least 50 % of the samples: FOSAA (11-127 ng/g), PFHpA (<0.04-115 ng/g), perfluorobutanesulfonic acid (PFBS) (<0.28-21 ng/g), PFOS (0.23-13 ng/g), perfluorotridecanoic acid (PFTrDA) (0.24-5.15 ng/g), perfluorododecanoic acid (PFDoDA) (<0.28-4.45 ng/g), perfluoroundecanoic acid (PFUnDA) (<0.28-2.33 ng/g), and 1H,1H,2H,2H-perfluorooctanesulfonic acid (6:2 FTSA) (0.07-1.01 ng/g). No significant differences were found for the concentrations of PFASs between calendar years and locations, but a slight increase could be observed in the sum concentration of PFASs (Æ©32PFASs) over the sampling years. As Tawny Owls are residential owls that usually do not cover great distances, their feathers can be used as a potential alternative matrix for future biomonitoring studies. To our knowledge, this is the first study on the occurrence of 32 PFASs investigated in feathers of a Tawny Owl population.

An uncanny case of paraneoplastic calcitriol mediated hypercalcaemia.

Summary: A 77-year-old female patient with a history of treated breast cancer and a recently diagnosed laryngeal cancer presented with severe hypercalcaemia associated with suppressed parathyroid hormone (PTH) levels. Her initial investigations included 25-hydroxy vitamin D levels, short synacthen test, bone scan, myeloma screen and thyroid function tests which were within normality. A computerised tomography (CT) scan showed some right lung apical fibrotic changes. Her PTH-related peptide (PTHrP) was normal and sarcoidosis was also excluded. Her previous and current malignancies were thought to be unlikely behind her hypercalcaemia. Her 1,25-dihydroxy vitamin D (calcitriol) levels were found to be elevated. Her hypercalcaemia was initially managed with intravenous fluids and intermittent bisphosphonates infusions which would transiently reduce her calcium levels. Steroid treatment was initiated which improved her hypercalcaemia; however, the calcium levels rebounded on tapering the steroids down, a pre-requisite prior to a positron emission computerised tomography (PET-CT) scan to determine the source of the excess calcitriol production. This was cancelled following an emergency admission with marked hypercalcaemia and acute renal and liver injury. A contemporary CT scan showed a right apical lung mass with hepatic lesions suggestive of a disseminated lung primary. The histology obtained from a liver biopsy was compatible with metastatic small-cell lung carcinoma. Unfortunately, her clinical condition deteriorated further and she did not survive. To the best of our knowledge, this is the first report in the literature describing calcitriol-mediated hypercalcaemia due to a small-cell lung cancer. Learning points: Paraneoplastic hypercalcaemia may manifest even without overt detection of the primary cancer. The workup for paraneoplastic hypercalcaemia should be meticulous. Both bisphosphonates and steroids are useful in the initial management of calcitriol-mediated hypercalcaemia, but the definitive management is the treatment of the cause.

Gene Expression Behavior of a Set of Genes in Platelet and Tissue Samples from Patients with Breast Cancer.

The tumor microenvironment (TME) is constituted by a great diversity of highly dynamic cell populations, each of which contributes ligands, receptors, soluble proteins, mRNAs, and miRNAs, in order to regulate cellular activities within the TME and even promote processes such as angiogenesis or metastasis. Intravasated platelets (PLT) undergo changes in the TME that convert them into tumor-educated platelets (TEP), which supports the development of cancer, angiogenesis, and metastasis through the degranulation and release of biomolecules. Several authors have reported that the deregulation of PF4, VEGF, PDGF, ANG-1, WASF3, LAPTM4B, TPM3, and TAC1 genes participates in breast cancer progression, angiogenesis, and metastasis. The present work aimed to analyze the expression levels of this set of genes in tumor tissues and platelets derived from breast cancer patients by reverse transcription-quantitative polymerase chain reaction (RTqPCR) assays, in order to determine if there was an expression correlation between these sources and to take advantage of the new information to be used in possible diagnosis by liquid biopsy. Data from these assays showed that platelets and breast cancer tumors present similar expression levels of a subset of these genes' mRNAs, depending on the molecular subtype, comorbidities, and metastasis presence.

Occurrence and tissue distribution of 33 legacy and novel per- and polyfluoroalkyl substances (PFASs) in Baikal seals (Phoca sibirica).

Per- and polyfluoroalkyl substances (PFASs) are bioaccumulative and associated with adverse effects in both wildlife and humans. The occurrence of 33 PFASs was assessed in the plasma, liver, blubber, and brain of 18 Baikal seals (Phoca sibirica) (16 pups and 2 adult females) from Lake Baikal, Russia (in 2011). Of the 33 congeners analysed for: perfluorooctanosulfonic acid (PFOS), 7 long chain perfluoroalkyl carboxylic acids (C8-C14 PFCAs) and 1 branched PFCA (perfluoro-3,7-dimethyloctanoic acid; P37DMOA) were most frequently detected. The PFASs in plasma and liver with the highest median concentrations were legacy congeners: perfluoroundecanoic acid (PFUnA; plasma: 11.2 ng/g w.w.; liver: 7.36 ng/g w.w.), PFOS (plasma: 8.67 ng/g w.w.; liver: 9.86 ng/g w.w.), perfluorodecanoic acid (PFDA; plasma: 5.13 ng/g w.w.; liver: 6.69 ng/g w.w.), perfluorononanoic acid (PFNA; plasma: 4.65 ng/g w.w.; liver: 5.83 ng/g w.w.) and perfluorotridecanoic acid (PFTriDA; plasma: 4.29 ng/g w.w.; liver: 2.55 ng/g w.w.). PFASs were detected in the brain of Baikal seals, indicating that PFASs cross through the blood-brain barrier. In blubber, the majority of PFASs were detected in low abundance and concentrations. In contrast to legacy PFASs, novel congeners (e.g., Gen X) were either detected infrequently or not found in Baikal seals. The worldwide occurrence of PFASs in pinnipeds was compared and lower median concentrations of PFOS were observed in Baikal seals relative to other pinnipeds. Conversely, similar concentrations of long chain PFCAs were found in Baikal seals compared to other pinnipeds. Furthermore, human exposure was assessed by estimating weekly intakes (EWI) of PFASs through Baikal seal consumption. Although PFASs concentrations were comparatively low relative to other pinnipeds, consumption of Baikal seal could exceed current regulatory guidelines.

Influence of Insertion Torques on the Surface Integrity in Different Dental Implants: An Ex Vivo Descriptive Study.

BACKGROUND: The primary objective of this ex vivo study was to assess the influence of increasing insertion torques on three types of dental implants and possible alterations of their microgeometry after the application of three different torque intensities. METHODS: 27 implants of 3 different implant brands (Groups A, B and C) were placed in cow ribs using 30 Ncm, 45 Ncm and 55 Ncm insertion torques. The implants were subsequently removed using trephine burs, and SEM analysis was carried out in order to detect implant surface and connection changes, as compared to the implant controls. RESULTS: Surface deformations were predominantly observed on the third apical part of the implants. The alterations presented with increasing insertion torques, with 45 Ncm being the threshold value. Prosthetic connections were also compromised. CONCLUSIONS: The changes sustained by the implants were proportional to the insertion torque they were subjected to; 45 Ncm and greater insertion torques resulted in more consistent damage, both on the implant surface and the implant connection.

Microalgae growth rate multivariable mathematical model for biomass production.

Background: The use of microalgae has been emerging as a potential technology to reduce greenhouse gases and bioremediate polluted water and produce high-value products as pigments, phytohormones, biofuels, and bioactive compounds. The improvement in biomass production is a priority to make the technology implementation profitable in every application mentioned before. Methods: The present study was conducted to explore the use of microalgae from genus Chlorella and Tetradesmus for the generation of substances of interest with UV absorption capacity. A mathematical model was developed for both microalgae to characterize the production of microalgae biomass considering the effects of light intensity, temperature, and nutrient consumption. The model was programmed in MATLAB software, where the three parameters were incorporated into a single specific growth rate equation. Results: It was found that the optimal environmental conditions for each genus (Chlorella T=36°C, and I<787 µmol/m2s; Tetradesmus T=23°C and I<150 µmol/m2s), as well as the optimal specific growth rate depending on the personalized values of the three parameters. Conclussion: This work could be used in the production of microalgae biomass for the design and development of topical applications to replace commercial options based on compounds that compromise health and have a harmful impact on the environment.

Analysis, occurrence and removal efficiencies of organophosphate flame retardants (OPFRs) in sludge undergoing anaerobic digestion followed by diverse thermal treatments.

Organophosphate flame retardants (OPFRs) are a complex group of contaminants to deal with in sewage sludge, as currently there is a lack of robust analytical methods to measure them and management strategies to remove them. To facilitate quantifications of the occurrence of OPFRs in sludge and to establish their removal efficiencies (REs%) during thermal treatments, a simple, reliable, and rapid sample preparation methodology was developed for the determination of 21 OPFRs in diverse sludge, ash and biochar matrices. Matrix-solid phase dispersion (MSPD) tailored to ultra-performance liquid chromatography (UPLC) coupled to tandem mass spectrometry (MS/MS) was applied. Under optimal conditions, 0.5 g of freeze-dried sample were dispersed in 2 g of Bondesil C18, and 1.5 g of deactivated florisil were used as clean-up sorbent. The target analytes were extracted with 5 mL of acetone. The obtained extract was ready for analysis within 20 min without the need of any further treatment. The proposed methodology was assessed, providing absolute recoveries (Abs%) ranging from 50.4 to 112 % with good method repeatability (RSDs <17.9 %). Method limits of quantification ranged from 0.10 to 14.0 ng g-1 dry weight (d.w.). The optimized methodology was applied to raw-, digested-, combusted and pyrolyzed sludge samples collected from different waste treatment plants located in Norway, where 16 out of 21 OPFRs were detected in digested sludge samples up to 2186 ng g-1 (d.w.; sum concentration of OPFRs). Diverse thermal treatments of combustion and dry pyrolysis were assessed for the removal of OPFRs from sludge. Combustion at 300 °C reduced the concentrations of OPFRs by 98 % (in the ashes formed), whereas pyrolysis at temperatures >500 °C effectively removed the OPFRs in the produced biochar. Thermal treatments, in particularly dry pyrolysis, showed potential for achieving zero pollution management and recycling of OPFR contaminated sludge.

Determination of steroid hormones in grey seal (Halichoerus grypus) blood plasma using convergence chromatography tandem mass spectrometry.

A hybrid solid phase extraction (HybridSPE) protocol tailored to ultra-performance convergence chromatography tandem mass spectrometry (UPC2-MS/MS) was developed for the determination of 19 steroid hormones in grey seal (Halichoerus grypus) blood plasma. In this study, the protocol demonstrated acceptable absolute recoveries ranging from 33 to 90%. The chromatographic separation was carried out using a gradient elution program with a total run time of 5 min. For most target analytes, the method repeatability ranged from 1.9 to 24% and the method limits of quantification (mLOQs) ranged from 0.03 to 1.67 ng/mL. A total of 9 plasma samples were analysed to demonstrate the applicability of the developed method, and 13 steroid hormones were quantified in grey seal pup plasma. The most prevalent steroids: cortisol, cortisone, corticosterone, 11-deoxycortisol, progesterone and 17α-hydroxyprogesterone were detected at concentrations in the range of 12.6-40.1, 7.10-24.2, 0.74-10.7, 1.06-5.72, 0.38-4.38 and

Therapeutic potential of progesterone in spinal cord injury-induced neuropathic pain: At the crossroads between neuroinflammation and N-methyl-D-aspartate receptor.

In recent decades, an area of active research has supported the notion that progesterone promotes a wide range of remarkable protective actions in experimental models of nervous system trauma or disease, and has also provided a strong basis for considering this steroid as a promising molecule for modulating the complex maladaptive changes that lead to neuropathic pain, especially after spinal cord injury. In this review, we intend to give the readers a brief appraisal of the main mechanisms underlying the increased excitability of the spinal circuit in the pain pathway after trauma, with particular emphasis on those mediated by the activation of resident glial cells, the subsequent release of proinflammatory cytokines and their impact on N-methyl-D-aspartate receptor function. We then summarize the available preclinical data pointing to progesterone as a valuable repurposing molecule for blocking critical cellular and molecular events that occur in the dorsal horn of the injured spinal cord and are related to the development of chronic pain. Since the treatment and management of neuropathic pain after spinal injury remains challenging, the potential therapeutic value of progesterone opens new traslational perspectives to prevent central pain.