Classification of Current Experimental Models of Epilepsy.

INTRODUCTION: This article provides an overview of several experimental models, including in vivo, genetics, chemical, knock-in, knock-out, electrical, in vitro, and optogenetics models, that have been employed to investigate epileptogenesis. The present review introduces a novel categorization of these models, taking into account the fact that the most recent classification that gained widespread acceptance was established by Fisher in 1989. A significant number of such models have become virtually outdated. OBJECTIVE: This paper specifically examines the models that have contributed to the investigation of partial seizures, generalized seizures, and status epilepticus. DISCUSSION: A description is provided of the primary features associated with the processes that produce and regulate the symptoms of various epileptogenesis models. Numerous experimental epilepsy models in animals have made substantial contributions to the investigation of particular brain regions that are capable of inducing seizures. Experimental models of epilepsy have also enabled the investigation of the therapeutic mechanisms of anti-epileptic medications. Typically, animals are selected for the development and study of experimental animal models of epilepsy based on the specific form of epilepsy being investigated. CONCLUSIONS: Currently, it is established that specific animal species can undergo epileptic seizures that resemble those described in humans. Nevertheless, it is crucial to acknowledge that a comprehensive assessment of all forms of human epilepsy has not been feasible. However, these experimental models, both those derived from channelopathies and others, have provided a limited comprehension of the fundamental mechanisms of this disease.

Incidence of haploidy and triploidy in trophectoderm biopsies of blastocysts derived from normally and abnormally fertilized oocytes.

PURPOSE: We aimed to identify the correlation between morphological pronuclear (PN) status and the genetically determined ploidy configuration in preimplantation embryos. METHODS: A retrospective observational study was conducted on 1982 embryos displaying normal fertilization and 380 embryos showing an atypical PN pattern, tested for aneuploidies and ploidy status via preimplantation genetic testing (PGT) between May 2019 and May 2024. Ploidy prediction was performed using a validated targeted-NGS approach and a proprietary bioinformatic pipeline analyzing SNPs B-allele frequency information. Ploidy results were obtained in relation to the morphological PN pattern and further stratified by mode of PN observation, maternal age, and embryo quality parameters. RESULTS: Abnormal ploidy results in 2PN-derived embryos were 1% (n = 20/1982): 0.8% showed triploidy and 0.2% haploidy. Ploidy results in relation to PN number in atypical fertilization were as follows: 0PN (n = 150/380) associated with 87.3% of diploidy, 8.7% of haploidy, and 4.0% of triploidy; 1PN-derived blastocysts (n = 73/153) were haploid in 47.7% of cases, 6.5% were triploid, and 45.7% diploid; 2.1PN (n = 23/280) and 3PN patterns (n = 54/280) predicted a triploid result in 34.8% and 74.1% of cases, respectively. PN observation with time-lapse increased ploidy status predictivity from 28.3% to 80.4% (p < 0.01) and reduced expected diploid rates to 19.6% (p < 0.01). Diploidy rate was higher for maternal age ≤ 35 years and for morphologically high-grade embryos. CONCLUSION: Morphological PN check can be improved by incorporating ploidy analysis within the conventional PGT workflow. Euploid 2PN-derived embryos can be further selected removing haploids and triploids, and some atypical PN pattern can be better classified.

Metal variability of the shrimp Palaemon elegans across coastal zones: anthropogenic and geological impacts.

This study focused on 120 specimens of the shrimp Palaemon elegans collected in intertidal zones in eight selected areas. This study aimed to assess the suitability of P. elegans as a bioindicator of natural and anthropogenic marine pollution. Metal concentrations of aluminum (Al), cadmium (Cd), copper (Cu), iron (Fe), lead (Pb), and zinc (Zn) were measured in shrimp collected from various sites in the Canary Islands, including areas affected by volcanic activity, industrial activity, and control zones. The determination of metal concentrations was conducted using inductively coupled plasma optical emission spectrophotometry (ICP-OES). The results showed significant differences in metal concentrations across the studied sites, with the highest levels of Al, Cu, Fe, Pb, and Zn observed in areas impacted by the Tajogaite volcanic eruption and harbor activity. Sites near old landfills and sewage pipes also exhibited elevated levels of Cd, Cu, and Pb, indicating strong anthropogenic influence. Al was found in the highest concentration in Harbour, reaching 25.7 ± 6.2 mg/kg, while the lowest concentration was observed in Control Lp at 11.5 ± 0.69 mg/kg. Conversely, lower metal concentrations were detected in control zones and areas with high dinoflagellate presence, suggesting a potential role of bioremediation by marine phytoplankton. The ability of P. elegans to accumulate metals in its tissues, particularly in areas of high pollution, highlights its potential as a bioindicator species. This study underscores the importance of P. elegans in monitoring marine pollution and provides insights into the environmental impact of both natural and human-induced contamination on coastal ecosystems.

Unraveling the ozone impact and oxidative stress on the nervous system.

Ozone (O3), a potent oxidant, can penetrate the body through breathing, generating reactive oxygen species (ROS) and triggering inflammatory processes. Oxidative stress, an imbalance between the production of ROS and the body's antioxidant capacity, plays a crucial role in the pathophysiology of various neurodegenerative diseases. This phenomenon can negatively impact the Central Nervous System (CNS), inducing structural and functional alterations that contribute to the development of neurological pathologies. This review examines how O3-induced oxidative stress affects the nervous system by analyzing existing literature on the involved molecular mechanisms and potential antioxidant systems to mitigate its effects. Through a comprehensive review of experimental studies, our objective is to shed light on the interaction between O3 and the nervous system, as well as its signaling pathways and altered genes, providing a foundation for future research in this field. Several studies have demonstrated that prolonged exposure to O3 leads to increased expression of reactive oxygen species, causing alterations in the blood-brain barrier and damage to astrocytes and microglia. These effects can lead to an increase in the production of proinflammatory cytokines, neurotoxins, and genes, exacerbating neuronal damage and accelerating the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and other neurological disorders. The results of this review suggest that exposure to O3 may induce oxidative damage to the nervous system, which could have significant implications for public health.

Severity of respiratory syncytial virus compared with SARS-CoV-2 and influenza among hospitalised adults ≥65 years.

INTRODUCTION: Our aim was to estimate the risk of pneumonia, admission to intensive care unit (ICU) or death in individuals ≥65 years old admitted to hospital with RSV, compared to influenza or COVID-19. METHODS: We included hospitalised patients from Severe Acute Respiratory Infection Surveillance in Spain between 2021-2024, aged ≥65 years, laboratory confirmed for RSV, influenza or SARS-CoV-2. Using a binomial regression with logarithmic link, we estimated the relative risk (RR) of pneumonia, ICU admission and in-hospital mortality, in patients with RSV compared to influenza or SARS-CoV-2, adjusting for age, sex, season and comorbidities. We stratified the estimates by vaccination status for influenza or SARS-CoV2. RESULTS: Among patients unvaccinated for influenza or SARS-CoV-2, those with RSV had similar or lower risk of pneumonia [vs. influenza: RR= 0.91 (95% Confidence Interval: 0.72-1.16); vs. SARS-CoV-2: 0.81 (0.67-0.98)], ICU admission [vs. influenza: 0.93 (0.41-2.08); vs. SARS-CoV-2: 1.10 (0.61-1.99)] and mortality [vs. influenza: 0.64 (0.32-1.28); vs. SARS-CoV-2: 0.56 (0.30-1.04)]. Among the vaccinated, results were largely similar except for a higher risk of ICU admission with RSV [vs. influenza: 2.13(1.16-3.89); vs. SARS-CoV-2: 1.83 (1.02-3.28)] CONCLUSIONS: RSV presented similar or lower intrinsic severity than influenza or SARS-CoV2. Among vaccinated patients, RSV was associated to higher ICU-admission, suggesting the potential for preventive RSV vaccination.

Human Exposure to Trace Elements (Al, B, Ba, Cd, Cr, Li, Ni, Pb, Sr, V) from Consumption of Dried Fruits Acquired in Spain.

Dried fruits are one of the most frequently consumed products by the population. Drying fruits prolongs their shelf life and also concentrates more nutrients. However, these products may contain dangerous levels of trace elements that can be harmful to health. The content of trace elements (Al, B, Ba, Cd, Cr, Li, Ni, Pb, Sr, V) in 42 samples of different dried fruits (dates, prunes, sultanas, dried apricot kernels, and dried figs) was determined by inductively coupled plasma spectrometry (ICP-OES). The concentrations of Al found in prunes (12.7 ± 5.13 mg Al/kg) and the concentrations of B found in dried plums (6.26 ± 4.45 mg B/kg) were significantly higher (p < 0.05). Regarding the risk assessment, the percentages of contribution to the maximum recommended intakes by Li in all the dried fruits studied stand out, reaching 35.3% in the case of dried plums. This study concludes that the recommended daily intake of dried fruit (30 g/day) does not pose a toxicological risk about these trace elements.

Lessons learned from 64,071 embryos subjected to PGT for aneuploidies: results, recurrence pattern and indications analysis.

RESEARCH QUESTION: What is the influence of biological, technical and clinical factors on embryo outcomes in preimplantation genetic testing for aneuploidies (PGT-A) and what is the recurrence pattern? DESIGN: This retrospective study included 64,071 embryos undergoing PGT-A in the same laboratory between 2011 and 2019. Biopsies were performed at the day 3 embryo stage (48.32%) or blastocyst stage (51.70%). Advanced maternal age (AMA) was the main indication (65.62%). RESULTS: The aneuploidy rate was 67.75%, higher in women aged over 35 years than in women aged 35 years or less (71.76% versus 47.44%), and higher in day 3 embryo versus blastocyst biopsies (77.51% versus 58.62%). The trisomy:monosomy ratio was 1.01 for blastocysts versus 0.84 for day 3 embryos. Trisomy 21 was present in 4.9% of embryos. In aneuploid embryos, the probability of having one or more involved chromosomes followed a decreasing exponential pattern. The probability of an embryo being euploid was constant at around 30% (40% in blastocysts, 20% in day 3 embryos). The cumulative probability of having one or more euploid embryos after 10 biopsied embryos was 94.79% in blastocysts and 80.61% in day 3 embryos. AMA was associated with a much higher aneuploidy rate than all other indications, which among them had similar aneuploidy rate and chromosomal involvement. CONCLUSIONS: There is a considerably lower aneuploidy rate in blastocysts than day 3 embryos, which is most notable for monosomies. While AMA shows an increased aneuploidy rate and a specific chromosomal pattern of involvement, the remaining indications showed a similar aneuploidy rate and chromosomal pattern. Even after producing many consecutive aneuploid embryos, the possibility of obtaining a euploid embryo is not negligible.

Metal variability in small pelagic fish Scomber colias as influenced by volcanic events in the Canary Islands.

Offshore volcanic activity occurs when an underwater volcano erupts. These volcanoes can be located underwater or on land and can be very dangerous to marine life. The aim of this study is to examine whether the influence of two volcanoes has an effect on the concentrations of metals and trace elements in the Atlantic mackerel Scomber colias in the Canary Islands. For the study, ten specimens of S. colias were obtained from each sampling area in March 2022. Metal concentrations were determined by inductively coupled plasma optical emission spectrophotometry (ICP-OES). The specimens of Scomber colias from the area affected by the Tajogaite volcano (La Palma) showed higher concentrations of all metals and trace elements analyzed than those from the other study areas. The specimens from the area of influence of the Tagoro Volcano (El Hierro) showed the second highest concentration of the elements studied, although this volcanic process is in a state of degassing.

The impact of implementing a non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) embryo culture protocol on embryo viability and clinical outcomes.

STUDY QUESTION: Are modifications in the embryo culture protocol needed to perform non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) affecting clinical reproductive outcomes, including blastocyst development and pregnancy outcomes? SUMMARY ANSWER: The implementation of an embryo culture protocol to accommodate niPGT-A has no impact on blastocyst viability or pregnancy outcomes. WHAT IS KNOWN ALREADY: The recent identification of embryo cell-free (cf) DNA in spent blastocyst media has created the possibility of simplifying PGT-A. Concerns, however, have arisen at two levels. First, the representativeness of that cfDNA to the real ploidy status of the embryo. Second, the logistical changes that need to be implemented by the IVF laboratory when performing niPGT-A and their effect on reproductive outcomes. Concordance rates of niPGT-A to invasive PGT-A have gradually improved; however, the impact of culture protocol changes is not as well understood. STUDY DESIGN, SIZE, DURATION: As part of a trial examining concordance rates of niPGT-A versus invasive PGT-A, the IVF clinics implemented a specific niPGT-A embryo culture protocol. Briefly, this involved initial culture of fertilized oocytes following each laboratory standard routine up to Day 4. On Day 4, embryos were washed and cultured individually in 10 µl of fresh media. On Day 6 or 7, blastocysts were then biopsied, vitrified, and media collected for the niPGT-A analysis. Six IVF clinics from the previously mentioned trial were enrolled in this analysis. In the concordance trial, Clinic A cultured all embryos (97 cycles and 355 embryos) up to Day 6 or 7, whereas in the remaining clinics (B-F) (379 cycles), nearly a quarter of all the blastocysts (231/985: 23.5%) were biopsied on Day 5, with the remaining blastocysts following the niPGT-A protocol (754/985: 76.5%). During the same period (April 2018-December 2020), the IVF clinics also performed standard invasive PGT-A, which involved culture of embryos up to Days 5, 6, or 7 when blastocysts were biopsied and vitrified. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 428 (476 cycles) patients were in the niPGT-A study group. Embryos from 1392 patients underwent the standard PGT-A culture protocol and formed the control group. Clinical information was obtained and analyzed from all the patients. Statistical comparisons were performed between the study and the control groups according to the day of biopsy. MAIN RESULTS AND THE ROLE OF CHANCE: The mean age, number of oocytes, fertilization rates, and number of blastocysts biopsied were not significantly different for the study and the control group. Regarding the overall pregnancy outcomes, no significant effect was observed on clinical pregnancy rate, miscarriage rate, or ongoing pregnancy rate (≥12 weeks) in the study group compared to the control group when stratified by day of biopsy. LIMITATIONS, REASONS FOR CAUTION: The limitations are intrinsic to the retrospective nature of the study, and to the fact that the study was conducted in invasive PGT-A patients and not specifically using niPGT-A cases. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that modifying current IVF laboratory protocols to adopt niPGT-A has no impact on the number of blastocysts available for transfer and overall clinical outcomes of transferred embryos. Whether removal of the invasive biopsy step leads to further improvements in pregnancy rates awaits further studies. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Igenomix. C.R., L.N.-S., and D.V. are employees of Igenomix. D.S. was on the Scientific Advisory Board of Igenomix during the study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03520933).

Effect of cannabidiol as a neuroprotective agent on neurodevelopmental impairment in rats with neonatal hypoxia.

OBJECTIVE: This study aims to investigate the neuroprotective effects of cannabidiol (CBD) on neurodevelopmental impairments in rats subjected to neonatal hypoxia, specifically examining its potential to mitigate motor and sensory deficits without the confounding effects of ischemia. METHODS: Neonatal Sprague-Dawley rats were allocated to one of four groups: Control, Control-CBD, Hypoxia, and Hypoxia-CBD. Hypoxia was induced on postnatal days 0 and 1. CBD (50 mg/kg) was administered orally for 14 days starting at postnatal day 0. Neurodevelopmental outcomes were assessed using the Neurodevelopmental Reflex Testing in Neonatal Rat Pups scale and the Revised Neurobehavioral Severity Scale for rodents. Statistical analyses were conducted using two-way and one-way ANOVA, with Tukey's post-hoc tests for group comparisons. RESULTS: Pup weights were recorded on specified postnatal days, with no significant differences observed across the groups (p = 0.1834). Significant neurological impairments due to hypoxia were noted in the Control group compared to the Hypoxia group, particularly in hindlimb grasping on postnatal day 3 (p = 0.0025), posture on postnatal day 12 (p = 0.0073), and in general balance and sound reflex on postnatal day 20 (p = 0.0016 and p = 0.0068, respectively). Additionally, a statistically significant improvement in posture was observed in the Hypoxia-CBD group compared to the Hypoxia group alone (p = 0.0024). CONCLUSION: Our findings indicate that CBD possesses neuroprotective properties that significantly counteract the neurodevelopmental impairments induced by neonatal hypoxia in rats. This study not only supports the therapeutic potential of CBD in managing conditions characterized by neurodevelopmental challenges due to hypoxia but also underscores the necessity for further investigation into the specific molecular mechanisms driving CBD's neuroprotective effects. Further research is essential to explore CBD's clinical applications and its potential role in treating human neurodevelopmental disorders.

Environmental Factors Influencing Metal Concentrations in Scomber colias Along the Canary Islands.

A total of 140 specimens of Scomber colias were collected from the Canary archipelago waters during the first semester of 2021, with 20 samples from each of the seven main islands. After analyzing the concentrations of metals (Al, Zn, Cd, Pb, Fe, and Cu) with ICP-OES, significant variations were observed among islands, with specimens from Tenerife and Gran Canaria containing higher levels of Al, Cd, and Pb, while those from Lanzarote and Fuerteventura had elevated levels of Zn, Fe, and Cu. These differences are probably related to greater anthropogenic activity around Tenerife and Gran Canaria coasts, leading to higher pollution levels, and the influence of Saharan dust and African upwelling on Lanzarote and Fuerteventura, enriching the waters with nutrients. Specific management strategies to mitigate marine pollution and continuous monitoring are crucial to safeguard marine ecosystems and to ensure food security.

Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis.

INTRODUCTION: Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs. MATERIALS AND METHODS: From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. RESULTS: In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection. CONCLUSION: SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.

Metal concentrations in echinoderms: Assessing bioindicator potential and ecological implications.

This study investigates the concentrations of heavy metals and trace elements in five echinoderm species: Holothuria (Platyperona) sanctori, Arbacia lixula, Coscinasterias tenuispina, Ophioderma longicaudum, and Antedon bifida. Given their ecological significance and potential as a food source, understanding the presence and transfer of heavy metals in these species is crucial. Sampling was conducted in 2022 in Canary Islands. Analysis using ICP-OES revealed concentrations of Zn, Cd, Pb, Cu, Ni, Cr, and Fe in mg/kg. The results showed a consistent sequence of metals across all species, with Fe > Zn > Cu > Ni > Cr > Pb > Cd. Holothurians exhibiting the highest levels, followed by sea urchins. Starfish and brittle stars showed similar, lower concentrations, while crinoids exhibited the lowest levels, consistent with their filter-feeding behavior. The findings highlight the potential of holothurians as bioindicators for environmental pollutants. Understanding the role of these echinoderms as bioindicators is essential for assessing ecosystem health and informing conservation efforts in subtropical marine environments.

Dosimetrical and geometrical parameters in single-fraction lattice radiotherapy for the treatment of bulky tumors: Insights from initial clinical experience.

PURPOSE: This study aims to investigate lattice radiotherapy (LRT) for bulky tumor in 10 patients, analyzing geometrical and dosimetrical parameters and correlations among variables. METHODS: Patients were prescribed a single-fraction of 18 Gy to 50 % of each spherical vertex (1.5 cm diameter). Vertices were arranged in equidistant planes forming a triangular pattern. Center-to-center distance (Dc-c) between vertices was varied from 4 to 5 cm. A new method for calculating the valley-to-peak dose ratio (VPDR) was proposed and compared to other two from existing literature. GTV volumes (VGTV), vertex number (Nvert), low-dose related parameters and vertex D99%, D50%, and D1% were recorded. Beam-on time and Monitor Units (MU) were also evaluated. Correlations were assessed using Spearman's coefficient, with significant differences analyzed using Mann-Whitney U test. RESULTS: Tumor volumes ranged from 417 to 3615 cm3. Median vertex number was 14.5 (IQR:11.3-17.8). VPDR ranged from 0.16 to 0.28. Median D99% spanned from 10.0 to 13.7 Gy, median D50% exceeded 18.0 Gy, and median D1% surpassed 23.3 Gy. Periphery dose remained under 4.0 Gy. Plans exhibited high modulation, with median beam-on time and MU of 8.8 min (IQR:8.2-10.1) and 13,069 MU (IQR:11574-13639). Significant correlations were found between Nvert and VGTV (p < 0.01), MU (p < 0.02) and beam-on time (p < 0.01) and between Dc-c and two VPDR definitions (p < 0.02) and periphery dose (p < 0.01). Significant differences were observed among the three valley dose definitions (p < 0.01) and the three peak dose definitions (p < 0.01). CONCLUSIONS: Reporting geometrical and dosimetrical parameters in LRT is crucial, alongside the need for unified definitions of valley and peak doses.

Metastatic Occult Primary Lobular Breast Cancer: A Case Report.

Breast cancer is the most common malignancy diagnosed in women. Invasive lobular breast cancer (ILC) is the second most common histologic subtype after invasive ductal carcinoma. Metastatic occult primary breast cancer, although rare, is a well-known clinical entity that usually presents with axillary lymphadenopathy without a detectable breast tumour. A perimenopausal woman in her 50s presented with abdominal pain, fatigue, and weight loss. Imaging showed peritoneal carcinomatosis with ascites, ovarian masses, and a lesion in the ascending colon. Gastric and colon biopsies showed infiltration from lobular breast cancer. Diagnostic workup, including mammography, breast ultrasound, and breast MRI, showed no evidence of breast pathology or axillary lymphadenopathy. First-line treatment with goserelin, letrozole, and palbociclib commenced with clinical improvement and radiological response. This case illustrates the challenges faced by clinicians in the diagnosis and treatment of lobular breast cancer without an identifiable primary lesion or axillary lymphadenopathy.

Culture time to optimize embryo cell-free DNA analysis for frozen-thawed blastocysts undergoing noninvasive preimplantation genetic testing for aneuploidy.

OBJECTIVE: To investigate the ideal time in culture to optimize embryo cell-free deoxyribonucleic acid (cfDNA) analysis in frozen-thawed blastocysts undergoing noninvasive preimplantation genetic testing for aneuploidy (PGT-A). Cell-free DNA is released into the spent blastocyst media (spent media) by the embryo. However, the optimal timing to determine maximal cfDNA in the case of frozen-thawed blastocysts undergoing noninvasive PGT-A remains to be elucidated. DESIGN: In this prospective observational study, 135 spent media and corresponding whole blastocysts were collected from January 2021 through March 2022. SETTING: Private fertility clinics. PATIENTS: Day-5 frozen-thawed blastocysts were cultured for 8 hours (Day-5 Short) or 24 hours (Day-5 Long), whereas day-6 frozen-thawed blastocysts were cultured for 8 hours (Day-6 Short). The spent media and whole blastocysts were then collected for further analysis. Spent media and whole blastocysts were amplified using whole genome amplification and sequenced using next-generation sequencing. MAIN OUTCOME MEASURES: Informativity and concordance rates between cfDNA in spent media and whole blastocyst DNA were compared according to the different times in culture. RESULTS: When comparing time in culture, informativity rates for spent media were significantly higher for Day-5 Long and Day-6 Short (>91%) compared with the Day-5 Short group (<60%). A similar trend was observed for cases with and without a previous PGT-A. Regarding blastocyst expansion grade, informativity rates were lower on Day-5 Short compared with Day-5 Long and Day-6 Short, regardless of expansion degree. This decrease was significant for Gardner-grade expansion grades 3, 4, and 5-6. In addition, for a similar time in culture, the grade of expansion did not have an impact on the informativity rates. For concordance rates, no significant differences were observed among the 3 groups. In all cases, concordance rates were 90.5% for Day-5 Short, 93.6% for Day-5 Long, and 92.3% for Day-6 Short. No impact of the expansion grade was observed on concordance rates. CONCLUSION: Noninvasive PGT-A in frozen-thawed blastocysts yields very high concordance rates with whole blastocysts, possibly limiting the need for invasive PGT-A and making it available for a wider range of patients.

Ultra-hypofractionated one-week locoregional radiotherapy for patients with early breast cancer: Acute toxicity results.

Purpose: Moderate hypofractionated radiotherapy is the standard of care for all patients with breast cancer, irrespective of stage or prior treatments. While extreme hypofractionation is accepted for early-stage tumours, its application in irradiating locoregional lymph nodes remains controversial. Materials and methods: A prospective registry analysis from July 2020 to September 2023 included 276 patients with early-stage breast cancer treated with one-week ultra-hypofractionation (UHF) at 26 Gy in 5 fractions on the whole breast (58.3 %) or thoracic wall (41.7 %) and ipsilateral regional lymph nodes and simultaneous integrated boost (58.3 %). Primary endpoint was assessment of acute adverse events (AEs). Secondarily, onset of early-delayed toxicity was assessed. A minimum 6-month follow-up was required for assessing potential treatment-related early-delayed complications. Acute or late complications attributable to treatment were assessed at inclusion using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Results: With a median follow-up of 19 months (range 1-49 months), 159 (57.6 %) patients reported AEs, predominantly grade (G) 1 (n = 139, 50.4 %) and G2 (n = 20, 7.8 %). Skin acute toxicity was common (G1/2: 134, G3: 14), while breast oedema occurred in 10 patients (G1: 9, G2: 1), and 15.9 % reported breast pain (G1: 42, G2: 2). Ipsilateral arm oedema was observed in 1.8 % patients. For patients with a follow-up beyond 6 months (n = 213), 23.4 % patients reported G1/G2 skin AEs, 8.8 % had G1/G2 breast/chest wall oedema, and 8.9 % experienced arm lymphedema. There were no cases of brachial plexopathy or G3 toxicity in this group of patients. Conclusions: One-week UHF adjuvant locoregional radiation is well-tolerated, displaying low-toxicity profiles comparable to other studies using similar irradiation schedules.

Exposure to Ozone Downregulates Bcl-2 and Increases Executing Caspases-3 and -8 in the Hippocampus, Frontal Cortex, and Cerebellum of Rats.

Introduction Ozone (O3) is one of the most prevalent atmospheric pollutants, arising from a photochemical reaction between volatile organic compounds (VOC), nitrogen oxides (NOx), and sunlight. O3 triggers oxidative stress, resulting in lipid oxidation, inflammation, alterations in metabolic and cellular signaling, and potentially initiating cell death in vulnerable brain regions. Inflammation and oxidative stress are recognized for their ability to induce cell death, primarily through the apoptosis pathway, involving various proteins that participate in this process via two pathways: intrinsic and extrinsic. Objective This study aims to identify the expression of pro-apoptotic proteins and Bcl-2 in the frontal cortex, cerebellum, and hippocampus of rats exposed to O3 acutely. Methods Two groups of 20 Wistar rodents (250-300 g) were established. The control group (n=10) was exposed to unrestricted polluted air for 12 hours, while the experimental group (n=10) was exposed to 1 ppm of O3. After exposure, the animals were sacrificed for immunofluorescence and Western blot analysis. Using a t-test, the arbitrary units of pro-apoptotic proteins and Bcl-2 were compared between the two groups. Results Significant increases in caspase-8 and caspase-3 activation were found in the O3-exposed group compared to the control group, specifically in the frontal cortex, cerebellum, and hippocampus. Additionally, notable changes in Bcl-2 expression were observed in these brain regions. The TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay further indicated significant differences in immunopositivity between the groups in the same areas. However, intrinsic apoptotic proteins such as Bax, VDAC1, and cytochrome-c did not show significant differences between the groups within these structures. Western blot analyses aligned with the immunofluorescence results, showing statistically significant concentrations of caspase-8 in the cerebellum, caspase-3 in the hippocampus, and Bcl-2 in the frontal cortex in the O3 exposed group. Conversely, proteins like Bax, cytochrome-c, and VDAC1 did not exhibit significant differences in all analyzed structures. Conclusions This study demonstrates that acute exposure to 1 ppm of ozone can trigger neuronal apoptosis in the frontal cortex, hippocampus, and cerebellum of rats, primarily through the activation of the extrinsic apoptosis pathway via caspase-8 and caspase-3. Additionally, it causes a reduction in Bcl-2 expression, an essential antiapoptotic protein. Despite not observing the activation of intrinsic pathway proteins like BAX, VDAC, or cytochrome-c, the study suggests that chronic O3 exposure might promote cell death by activating this pathway, requiring further long-term research.

Impact of natural events on metal bioaccumulation in Anemonia sulcata.

Samples of Anemonia sulcata were collected in 2022 from different areas of the Canary Islands affected by different natural contamination sources, such sandstorms, submarine volcanic activity, continuous rainfall, upwelling and dinoflagellate blooms. Significant differences were observed between the zones for the metals and trace elements analyzed (Al, Zn, Cd, Pb, Ni, Co, Fe, B, Cu, Mg and Li). Anemones from volcanic areas showed higher levels of Cd, Pb and Ni. Individuals from sandstorm areas showed elevated levels of Al, Zn and Fe. Samples collected from areas affected by upwelling processes had higher concentrations of Cu, Mg and Li. Finally, the areas affected by dinoflagellates showed lower levels of Zn, Pb, Fe, Mg and Li. The study reveals how natural phenomena dramatically influence metal accumulation in A. sulcata, which is of great value for anticipating and managing potential problems associated with public health.

Comparative analysis of metal pollution in the Atlantic Ocean and Mediterranean Sea: insights from Anemonia sulcata study.

In this study, we investigated metal concentrations in Anemonia sulcata specimens from various locations in the Atlantic Ocean and the Mediterranean Sea. A total of 84 individuals were sampled from specific zones, and their tissue samples were processed for metal analysis using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The results revealed notable differences in metal concentrations among the studied regions. The Atlantic Ocean and the Mediterranean Sea were found to have distinct patterns of marine pollution, influenced by a complex interplay of geographical, demographic, industrial, and environmental policy factors. Conversely, the semi-enclosed Mediterranean Sea has a lower natural dilution capacity, leading to the accumulation and prolonged presence of pollutants. Population density and industrial activities in coastal areas play a significant role in pollution disparities between the Mediterranean Sea and the Atlantic Ocean. The Mediterranean coasts, with higher population densities and intensive industrial operations, experience greater strain on marine ecosystems due to increased pollution sources. Additionally, environmental policies and management approaches differ between the two regions, contributing to variations in pollution response and regulation.