Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans.

Spinal cord injury results in the loss of sensory, motor, and autonomic functions, which almost always produces permanent physical disability. Thus, in the search for more effective treatments than those already applied for years, which are not entirely efficient, researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach, seeking to promote neuronal recovery after spinal cord injury. Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and, consequently, boosting functional recovery. Although the majority of experimental research has been conducted in rodents, there is increasing recognition of the importance, and need, of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans. This article is a literature review from databases (PubMed, Science Direct, Elsevier, Scielo, Redalyc, Cochrane, and NCBI) from 10 years ago to date, using keywords (spinal cord injury, cell therapy, non-human primates, humans, and bioengineering in spinal cord injury). From 110 retrieved articles, after two selection rounds based on inclusion and exclusion criteria, 21 articles were analyzed. Thus, this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans, aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Exploring Functional Products and Early-Life Dynamics of Gut Microbiota.

Research on the microbiome has progressed from identifying specific microbial communities to exploring how these organisms produce and modify metabolites that impact a wide range of health conditions, including gastrointestinal, metabolic, autoimmune, and neurodegenerative diseases. This review provides an overview of the bacteria commonly found in the intestinal tract, focusing on their main functional outputs. We explore biomarkers that not only indicate a well-balanced microbiota but also potential dysbiosis, which could foreshadow susceptibility to future health conditions. Additionally, it discusses the establishment of the microbiota during the early years of life, examining factors such as gestational age at birth, type of delivery, antibiotic intake, and genetic and environmental influences. Through a comprehensive analysis of current research, this article aims to enhance our understanding of the microbiota's foundational development and its long-term implications for health and disease management.

Healthcare and Epidemiological Surveillance Costs of Hepatitis A Outbreaks in Spain in Regions with and without Universal Hepatitis A Vaccination of Children during 2010-2018.

The aim of this study was to evaluate and compare hepatitis A outbreak-associated healthcare and epidemiological surveillance costs in Spain in two types of autonomous regions during 2010-2018: (1) regions with a prevention strategy based on universal hepatitis A vaccination of children and vaccination of high-risk population groups (Catalonia) and (2) regions with a prevention strategy based on vaccinating high-risk population groups (Castile and Leon, Murcia, Navarra, Community of Madrid, Community of Valencia). Healthcare costs were determined based on the resources used to treat hepatitis A outbreak-associated cases and hospitalizations. Epidemiological surveillance costs were calculated from the resources used during surveillance activities. The ratios for total, healthcare and epidemiological surveillance costs (regions without universal hepatitis A vaccination of children vs. Catalonia) were used to compare the two hepatitis A prevention strategies. From 2010 to 2018, the total, healthcare and epidemiological surveillance costs per million population were 1.75 times (EUR 101,671 vs. EUR 58,032), 1.96 times (EUR 75,500 vs. EUR 38,516) and 1.34 times greater (EUR 26,171 vs. EUR 19,515) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. The ratios tended to increase over time during 2010-2018. In 2015-2018, total, healthcare and epidemiological surveillance costs per million population were 2.68 times (EUR 69,993 vs. EUR 26,158), 2.86 times (EUR 53,807 vs. EUR 18,825) and 2.21 times greater (EUR 16,186 vs. EUR 7333) in regions without universal hepatitis A vaccination of children than in Catalonia, respectively. These findings suggest that universal hepatitis A vaccination of children could reduce hepatitis A outbreak-associated costs.

Enhanced Learning and Memory in Patients with CRB1 Retinopathy.

Mutations in the CRB1 gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The CRB1 gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition has not been described before. This study compares cognitive function in CRB1 retinopathy individuals with subjects with other retinopathies and the normal population. METHODS: Neuropsychological tests of cognitive function were used to test individuals with CRB1 and non-CRB1 retinopathies and compare results with a standardised normative dataset. RESULTS: CRB1 retinopathy subjects significantly outperformed those with non-CRB1 retinopathy in list learning tasks of immediate (p = 0.001) and delayed memory (p = 0.007), tests of semantic verbal fluency (p = 0.017), verbal IQ digit span subtest (p = 0.037), and estimation test of higher execution function (p = 0.020) but not in the remaining tests of cognitive function (p > 0.05). CRB1 retinopathy subjects scored significantly higher than the normal population in all areas of memory testing (p < 0.05) and overall verbal IQ tests (p = 0.0012). Non-CRB1 retinopathy subjects scored significantly higher than the normal population in story recall, verbal fluency, and overall verbal IQ tests (p = 0.0016). CONCLUSIONS: Subjects with CRB1 retinopathy may have enhanced cognitive function in areas of memory and learning. Further work is required to understand the role of CRB1 in cognition.

End-of-life care needs in cancer patients: a qualitative study of patient and family experiences.

BACKGROUND: Cancer is a disease that transcends what is purely medical, profoundly affecting the day-to-day life of both patients and family members. Previous research has shown that the consequences of cancer are greatly aggravated in patients at the end of life, at a time when they must also grapple with numerous unmet needs. The main objective of this study was to obtain more in-depth insight into these needs, primarily in patients with end-stage cancer nearing death. METHODS: Semi-structured interviews were conducted in Spain with cancer patients at the end of life (n = 3) and their family members (n = 12). The findings from the interviews were analyzed using qualitative thematic analysis and a grounded theory approach. RESULTS: Four major themes emerged from the interviews that explored the needs and concerns of patients with cancer at the end of life: (1) physical well-being (2) emotional well-being (3) social well-being and (4), needs relating to information and autonomous decision-making. The interviews also shed light on the specific needs of family members during this period, namely the difficulties of managing increased caregiver burden and maintaining a healthy work-life balance. CONCLUSIONS: A lack of support, information and transparency during a period of immense vulnerability makes the end-of-life experience even more difficult for patients with cancer. Our findings highlight the importance of developing a more in-depth understanding of the needs of this population, so that informed efforts can be made to improve palliative healthcare and implement more comprehensive care and support at the end of life.

Nanoarchitecture of CaV2.1 channels and GABAB receptors in the mouse hippocampus: Impact of APP/PS1 pathology.

Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to synaptic plasticity and to processes such as learning and memory. Despite their recognized importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Here, we aimed to explore the impact of AD pathology on the density and nanoscale compartmentalization of CaV2.1 channels in the hippocampus in association with GABAB receptors. Histoblotting experiments showed that the density of CaV2.1 channel was significantly reduced in the hippocampus of APP/PS1 mice in a laminar-dependent manner. CaV2.1 channel was enriched in the active zone of the axon terminals and was present at a very low density over the surface of dendritic tree of the CA1 pyramidal cells, as shown by quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL). In APP/PS1 mice, the density of CaV2.1 channel in the active zone was significantly reduced in the strata radiatum and lacunosum-moleculare, while it remained unaltered in the stratum oriens. The decline in Cav2.1 channel density was found to be associated with a corresponding impairment in the GABAergic synaptic function, as evidenced by electrophysiological experiments carried out in the hippocampus of APP/PS1 mice. Remarkably, double SDS-FRL showed a co-clustering of CaV2.1 channel and GABAB1 receptor in nanodomains (~40-50 nm) in wild type mice, while in APP/PS1 mice this nanoarchitecture was absent. Together, these findings suggest that the AD pathology-induced reduction in CaV2.1 channel density and CaV2.1-GABAB1 de-clustering may play a role in the synaptic transmission alterations shown in the AD hippocampus. Therefore, uncovering these layer-dependent changes in P/Q calcium currents associated with AD pathology can benefit the development of future strategies for AD management.

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.

Paxlovid™ reduces the incidence of pneumonia, hospitalization, and death in a cohort of COVID-19 patients from northeast Mexico.

BACKGROUND: Information on Paxlovid™ effectiveness must be monitored and updated in real world scenarios. Our research question was what is the effectiveness of Paxlovid™ in adult patients with COVID-19? Therefore, we investigated the effectiveness of Paxlovid™ on reducing the incidence of pneumonia, hospitalization, and mortality in a cohort of COVID-19 positive adult patients from northeast Mexico. METHODS: A retrospective cohort study of COVID-19 positive adult patients from Nuevo Leon, Mexico from December 2020 to May 2023 (after Omicron BA-5 circulation) was performed. Paxlovid™ use was authorized in September 2022. Therefore, we analyzed effectiveness in patients with confirmed diagnosis who met selection criteria between September 2022 and May 2023 (n = 20,799; 5,673 with and 15,126 without Paxlovid™). RESULTS: The pneumonia (0.1% vs. 0.4%, p < 0.0001), hospitalization (0.1% vs. 1.2%, p < 0.0001), and death rates (0.04% vs. 0.2%, p < 0.0001) were lower in patients with Paxlovid™ treatment independently of age, sex, comorbidity, and COVID-19 and pneumococcal vaccination history. Effectiveness was 88.2%, 95.9% y 91.9% for pneumonia, hospitalization, and death, respectively. CONCLUSIONS: Paxlovid™ reduces the presentation of pneumonia, hospitalization, and death secondary to COVID-19. It is recommended to continue monitoring Paxlovid™ effectiveness, as other SARS-CoV-2 variants continue to emerge.

Spin crossover {[Fe(atrz)3](OTs)2}n monolith: a green synthesis approach for Robust switchable materials.

This work presents a straightforward, room-temperature synthesis of a robust {[Fe(atrz)3](OTs)2}n monolith. This approach offers a green alternative to traditional nanoparticle synthesis for manipulating spin crossover (SCO) behaviour. The monolith exhibits a more gradual SCO transition at lower temperatures compared to the bulk material, aligning with observations in smaller particle systems. Notably, the synthesis employs a solvent- and surfactant-free approach, simplifying the process and potentially reducing environmental impact, aligning with the principles of green chemistry.

Prevalence and outcomes of fear of falling in older adults with falls at the emergency department: a multicentric observational study.

PURPOSE: Fear of falling (FOF) may result in activity restriction and deconditioning. The aim of the study was to identify factors associated with FOF in older patients and to investigate if FOF influenced long-term outcomes. METHODS: Multicentric, observational, prospective study including patients 65 years or older attending the emergency department (ED) after a fall. Demographical, patient- and fall-related features were recorded at the ED. FOF was assessed using a single question. The primary outcome was all-cause death. Secondary outcomes included new fall-related visit, fall-related hospitalisation, and admission to residential care. Logistic regression and Cox regression models were used for statistical analyses. RESULTS: Overall, 1464 patients were included (47.1% with FOF), followed for a median of 6.2 years (2.2-7.9). Seven variables (age, female sex, living alone, previous falls, sedative medications, urinary incontinence, and intrinsic cause of the fall) were directly associated with FOF whereas use of walking aids and living in residential care were inversely associated. After the index episode, 748 patients (51%) died (median 3.2 years), 677 (46.2%) had a new fall-related ED visit (median 1.7 years), 251 (17.1%) were hospitalised (median 2.8 years), and 197 (19.4%) were admitted to care (median 2.1 years). FOF was associated with death (HR 1.239, 95% CI 1.073-1.431), hospitalisation (HR 1.407, 95% CI 1.097-1.806) and institutionalisation (HR 1.578, 95% CI 1.192-2.088), but significance was lost after adjustment. CONCLUSION: FOF is a prevalent condition in older patients presenting to the ED after a fall. However, it was not associated with long-term outcomes. Future research is needed to understand the influence of FOF in maintenance of functional capacity or quality of life.

Utility of time in tight range (TITR) in evaluating metabolic control in pediatric and adult patients with type 1 diabetes in treatment with advanced hybrid closed-loop systems.

PURPOSE: To analyze the time in tight range (TITR), and its relationship with other glucometric parameters in patients with type 1 diabetes (T1D) treated with advanced hybrid closed-loop (AHCL) systems. METHODS: A prospective observational study was conducted on pediatric and adult patients with T1D undergoing treatment with AHCL systems for at least 3 months. Clinical variables and glucometric parameters before and after AHCL initiation were collected. RESULTS: A total of 117 patients were evaluated. Comparison of metabolic control after AHCL initiation showed significant improvements in HbA1c (6.9 ± 0.9 vs. 6.6 ± 0.5%, p < 0.001), time in range (TIR) (68.2 ± 11.5 vs. 82.5 ± 6.9%, p < 0.001), TITR (43.7 ± 10.8 vs. 57.3 ± 9.7%, p < 0.001), glucose management indicator (GMI) (6.9 ± 0.4 vs. 6.6 ± 0.3%, p < 0.001), time below range (TBR) 70-54 mg/dl (4.3 ± 4.5 vs. 2.0 ± 1.4%, p < 0.001), and time above range (TAR) > 180 mg/dl (36.0 ± 7.6 vs. 15.1 ± 6.4%, p < 0.001). Coefficient of variation (CV) also improved (36.3 ± 5.7 vs. 30.6 ± 3.7, p < 0.001), while time between 140-180 mg/dl remained unchanged. In total, 76.3% achieved TITR > 50% (100% pediatric). Correlation analysis between TITR and TIR and GRI showed a strong positive correlation, modified by glycemic variability. CONCLUSIONS: AHCL systems achieve significant improvements in metabolic control (TIR > 70% in 93.9% patients). The increase in TIR was not related to an increase in TIR 140-180 mg/dl. Despite being closely related to TIR, TITR allows for a more adequate discrimination of the achieved control level, especially in a population with good initial metabolic control. The correlation between TIR and TITR is directly influenced by the degree of glycemic variability.

Impact of the Universal Implementation of Adolescent Hepatitis B Vaccination in Spain.

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; p < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; p = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; p < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.

Burning Mouth Syndrome Treated with Low-Level Laser and Clonazepam: A Randomized, Single-Blind Clinical Trial.

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic pain disorder characterized by intraoral burning or dysaesthetic sensation, with the absence of any identifiable lesions. Numerous treatments for BMS have been investigated, though without conclusive results. An analysis was conducted of the efficacy of treatment with a low-level diode laser and clonazepam in patients with BMS, and a study was carried out on the levels of different salivary biomarkers before and after treatment. MATERIAL AND METHODS: A randomized, single-blind clinical trial was carried out involving 89 patients divided into the following groups: group 1 (laser, The Helbo® Theralite Laser 3D Pocket Probe + clonazepam) (n = 20), group 2 (sham laser placebo) (n = 19), group 3 (laser) (n = 21) and group 4 (clonazepam) (n = 18). Symptom intensity was scored based on a visual analogue scale (VAS). Sialometry was performed before and after treatment, and the Xerostomia Inventory, Oral Health Impact Profile-14 (OHIP-14) and Mini-Nutritional Assessment (MNA) questionnaires were administered. The following markers were measured in saliva samples: interleukins (IL2, IL4, IL5, IL6, IL7, IL8, IL1ß, IL10, IL12, IL13, IL17, IL21 and IL23), proteins (MIP-3α, MIP-1α and MIP-1ß), GM-CSF, interferon gamma (IFNγ), interferon-inducible T-cell alpha chemoattractant (ITAC), fractalkine and tumor necrosis factor α (TNFα). RESULTS: A significant decrease in the VAS scores was observed after treatment in group 1 (laser + clonazepam) (p = 0.029) and group 3 (laser) (p = 0.005). In turn, group 3 (laser) showed a decrease in the salivary concentration of fractalkine (p = 0.025); interleukins IL12 (p = 0.048), IL17 (p = 0.020), IL21 (p = 0.008), IL7 (p = 0.001) and IL8 (p = 0.007); proteins MIP1α (p = 0.048) and MIP1ß (p = 0.047); and TNFα (p = 0.047) versus baseline. Following treatment, group 1 (laser + clonazepam) showed significant differences in IL21 (p = 0.045) and IL7 (p = 0.009) versus baseline, while group 4 (clonazepam) showed significant differences in IL13 (p = 0.036), IL2 (p = 0.020) and IL4 (p = 0.001). No significant differences were recorded in group 2 (sham laser placebo). CONCLUSIONS: The low-level diode laser is a good treatment option in BMS, resulting in a decrease in patient symptoms and in salivary biomarkers. However, standardization of the intervention protocols and laser intensity parameters is needed in order to draw more firm conclusions.

Efficacy of conduction hyperthermia in the treatment of non-muscle invasive bladder cancer: A systematic review.

INTRODUCTION: Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy. OBJECTIVE: To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC. MATERIAL AND METHODS: The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety. RESULTS: Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences. CONCLUSIONS: Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions.

Galectin-3 absence alters lymphocytes populations dynamics behavior and promotes functional recovery after spinal cord injury in mice.

Spinal cord injury (SCI) results from various mechanisms that damage the nervous tissue and the blood-brain barrier, leading to sensory and motor function loss below the injury site. Unfortunately, current therapeutic approaches for SCI have limited efficacy in improving patients outcomes. Galectin-3, a protein whose expression increases after SCI, influences the neuroinflammatory response by favoring pro-inflammatory M1 macrophages and microglia, while inhibiting pro-regenerative M2 macrophages and microglia, which are crucial for inflammation resolution and tissue regeneration. Previous studies with Galectin-3 knock-out mice demonstrated enhanced motor recovery after SCI. The M1/M2 balance is strongly influenced by the predominant lymphocytic profiles (Th1, Th2, T Reg, Th17) and cytokines and chemokines released at the lesion site. The present study aimed to investigate how the absence of galectin-3 impacts the adaptive immune system cell population dynamics in various lymphoid spaces following a low thoracic spinal cord compression injury (T9-T10) using a 30 g vascular clip for one minute. It also aimed to assess its influence on the functional outcome in wild-type (WT)and Galectin-3 knock-out (GALNEG) mice. Histological analysis with hematoxylin-eosin and Luxol Fast Blue staining revealed that WT and GALNEG animals exhibit similar spinal cord morphology. The absence of galectin-3 does not affect the common neuroanatomy shared between the groups prompting us to analyze outcomes between both groups. Following our crush model, both groups lost motor and sensory functions below the lesion level. During a 42-day period, GALNEG mice demonstrated superior locomotor recovery in the Basso Mouse Scale (BMS) gait analysis and enhanced motor coordination performance in the ladder rung walk test (LRW) compared to WT mice. GALNEG mice also exhibited better sensory recovery, and their electrophysiological parameters suggested a higher number of functional axons with faster nerve conduction. Seven days after injury, flow cytometry of thymus, spleen, and blood revealed an increased number of T Reg and Th2 cells, accompanied by a decrease in Th1 and Th17 cells in GALNEG mice. Immunohistochemistry conducted on the same day exhibited an increased number of Th2 and T Reg cells around the GALNEG's spinal cord lesion site. At 42-day dpi immunohistochemistry analyses displayed reduced astrogliosis and greater axon preservation in GALNEG's spinal cord seem as a reduction of GFAP immunostaining and an increase in NFH immunostaining, respectively. In conclusion, GALNEG mice exhibited better functional recovery attributed to the milder pro-inflammatory influence, compensated by a higher quantity of T Reg and Th2 cells. These findings suggest that galectin-3 plays a crucial role in the immune response after spinal cord injury and could be a potential target for clinical therapeutic interventions.

First Detection of Algal Caribbean Ciguatoxin in Amberjack Causing Ciguatera Poisoning in the Canary Islands (Spain).

Ciguatera Poisoning (CP) is an illness associated with the consumption of fish contaminated with potent natural toxins found in the marine environment, commonly known as ciguatoxins (CTXs). The risk characterization of CP has become a worldwide concern due to the widespread expansion of these natural toxins. The identification of CTXs is hindered by the lack of commercially available reference materials. This limitation impedes progress in developing analytical tools and conducting toxicological studies essential for establishing regulatory levels for control. This study focuses on characterizing the CTX profile of an amberjack responsible for a recent CP case in the Canary Islands (Spain), located on the east Atlantic coast. The exceptional sensitivity offered by Capillary Liquid Chromatography coupled with High-Resolution Mass Spectrometry (cLC-HRMS) enabled the detection, for the first time in fish contaminated in the Canary Islands, of traces of an algal ciguatoxin recently identified in G. silvae and G. caribeaus from the Caribbean Sea. This algal toxin was structurally characterized by cLC-HRMS being initially identified as C-CTX5. The total toxin concentration of CTXs was eight times higher than the guidance level proposed by the Food and Drug Administration (0.1 ng C-CTX1/g fish tissue), with C-CTX1 and 17-hydroxy-C-CTX1 as major CTXs.

Diagnostic Methods for the Prenatal Detection of Cleft Lip and Palate: A Systematic Review.

Background: Accurate prenatal diagnosis of cleft lip and palate is essential to discuss severity prediction, perform appropriate parental counseling, and, at last, establish long-term treatment planning. The aim of this systematic review was to analyze the accuracy of various imaging techniques for the prenatal diagnosis of cleft lip and palate, assess the pregnancy phase for orofacial clefts diagnosis, and study the different cleft types in terms of diagnostic methods, timing, and predictability. Methods: A search of the PubMed, EMBASE, Scopus, and Web of Science databases was conducted to identify potentially relevant studies published until January 2024. The quality of the selected articles was assessed using the Newcastle-Ottawa scale for methodological quality assessment of cohort studies and the QUADAS-2 scale for diagnostic test studies. Results: A total of 18 studies met the eligibility criteria and were included in the review. The findings of this review indicate that the majority of studies showed improved diagnostic accuracy when supplementary techniques, such as 3D ultrasound or magnetic resonance imaging, were added to 2D ultrasound. Conclusions: The implementation of magnetic resonance imaging as a standard procedure could significantly improve the precision of diagnosing cleft lip and palate. Therefore, the diagnostic technique used will play a crucial role in the accuracy of the diagnosis.

Human mesenchymal stromal cells-laden crosslinked hyaluronic acid-alginate bioink for 3D bioprinting applications in tissue engineering.

Three-dimensional (3D) bioprinting is considered one of the most advanced tools to build up materials for tissue engineering. The aim of this work was the design, development and characterization of a bioink composed of human mesenchymal stromal cells (hMSC) for extrusion through nozzles to create these 3D structures that might potentially be apply to replace the function of damaged natural tissue. In this study, we focused on the advantages and the wide potential of biocompatible biomaterials, such as hyaluronic acid and alginate for the inclusion of hMSC. The bioink was characterized for its physical (pH, osmolality, degradation, swelling, porosity, surface electrical properties, conductivity, and surface structure), mechanical (rheology and printability) and biological (viability and proliferation) properties. The developed bioink showed high porosity and high swelling capacity, while the degradation rate was dependent on the temperature. The bioink also showed negative electrical surface and appropriate rheological properties required for bioprinting. Moreover, stress-stability studies did not show any sign of physical instability. The developed bioink provided an excellent environment for the promotion of the viability and growth of hMSC cells. Our work reports the first-time study of the effect of storage temperature on the cell viability of bioinks, besides showing that our bioink promoted a high cell viability after being extruded by the bioprinter. These results support the suggestion that the developed hMSC-composed bioink fulfills all the requirements for tissue engineering and can be proposed as a biological tool with potential applications in regenerative medicine and tissue engineering.

Radiopharmaceuticals Adverse Events Management.

BACKGROUND AND PURPOSE: Radiopharmaceuticals are radioactive compounds used for diagnostic or therapeutic purposes which are most often administered intravenously. Adverse events that may induce both adverse reactions and drug-to-drug interactions with changes in expected biodistribution, potentially affecting patient safety and diagnostic accuracy. Adverse reactions are relatively rare due to the small doses and under-reporting is the norm. The aim of this study is to increase awareness of the need to report in order to create protocols for the management of such adverse events among professionals in a Nuclear Medicine Department. METHODS: A reporting system was established a decade ago through an electronic form to enhance adverse event registration. The radiopharmacist collects data for further communication with National Health authorities and develops an annual report with recommendations on the management of these adverse events. RESULTS: A total of 128 reports were collected, including 65 cases of extravasations, 18 adverse reactions, and 45 drug interactions. Over the years, reporting has been increasing, adverse reactions occurred at a higher incidence than reported in the literature, and each anomalous biodistribution was analysed for possible drug interaction. The annual reports have been used to develop a local guideline for the management of adverse reactions and recommendations for discontinuation of treatment to avoid interactions with radiopharmaceuticals. CONCLUSION: The recognition of adverse events associated with radiopharmaceuticals is increasing, underlining the need for vigilant reporting and improved management strategies. An efficient reporting system promotes awareness of possible interactions between radiopharmaceuticals and other medicines and their potential adverse reactions to enhance patient safety.

Designing multitarget ligands for neurodegenerative diseases with improved permeability trough PLGA nanoencapsulation.

Multitarget ligands (MTLs) have emerged as an interesting alternative for addressing complex multifactorial pathologies such as neurodegenerative diseases. However, a common challenge associated with these compounds is often their high molecular weight and low solubility, which becomes a hurdle when trying to permeate over the blood-brain barrier (BBB). In this study, we have designed two new MTLs that modulate three pharmacological targets simultaneously (tau, beta-amyloid and TAR DNA-binding protein 43). To enhance their brain penetration, we have formulated organic polymeric nanoparticles using poly(lactic-co-glycolic acid). The characterization of the formulations, evaluation of their permeability through an in vitro BBB model, and assessment of their activity on disease-representative cellular models, such as Alzheimer's disease and amyotrophic lateral sclerosis, have been conducted. The results demonstrate the potential of the new MTLs and their nanoparticle encapsulation for the treatment of neurodegenerative diseases.