Current Trends and Advancements in the Management of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a significant global health burden with a high mortality rate. Over the past 40 years, significant progress has been achieved in the prevention and management of HCC. SUMMARY: Hepatitis B vaccination programs, the development of direct acting antiviral drugs for Hepatitis C, and effective surveillance strategies provide a profound basis for the prevention of HCC. Advanced surgery and liver transplantation along with local ablation techniques potentially offer cure for the disease. Also, just recently, the introduction of immunotherapy opened a new chapter in systemic treatment. Finally, the introduction of the BCLC classification system for HCC, clearly defining patient groups and assigning reasonable treatment options, has standardized treatment and become the basis of almost all clinical trials for HCC. With this review, we provide a comprehensive overview of the evolving landscape of HCC management and also touch on current challenges. KEY MESSAGE: A comprehensive and multidisciplinary approach is crucial for effective HCC management. Continued research and clinical trials are imperative to further enhance treatment options and will ultimately reduce the global burden of this devastating disease.

Pituitary metastasis arising from hepatocellular carcinoma: a case report and update of the literature.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined.

Effects of Voluntary Physical Exercise on the Neurovascular Unit in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.

Alzheimer's Disease: An Updated Overview of Its Genetics.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1-5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or the Amyloid precursor protein (APP). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aß) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.

Chlorhexidine residues in sludge from municipal wastewater treatment plants: analytical determination and toxicity evaluation.

In this work, a procedure for the sensitive and selective determination of chlorhexidine in sludge from municipal sewage treatment plants (STPs) based on matrix solid-phase dispersion (MSPD) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was optimized and validated. Analysis of sewage sludge samples, obtained from different STPs in Northwest Spain from 2018 to 2021, showed that chlorhexidine was ubiquitous in this environmental compartment with concentrations between 0.3 and 16 µg g-1. The toxicity of this pollutant was assessed in in vitro assays considering three different model organisms: Candida albicans, Escherichia coli, and Staphylococcus aureus. C. albicans was the most sensitive of the tested microorganisms to chlorhexidine with a lethal threshold concentration of 0.1 mg L-1. Thus, the lowest observed sludge residue was 3 times higher than the acute toxicity threshold measured for C. albicans. Moreover, E. coli and S. aureus were also affected at chlorhexidine concentrations around 1.8 mg L-1 and 0.5 mg L-1, respectively. So, chlorhexidine residues might affect the population of microorganisms existing in STPs. In addition, the potential phytotoxicity of the compound was evaluated with germination experiments using different model seeds. At the evaluated dose (10 µg g-1 dried soil), chlorhexidine did not affect the germination of Sorghum saccharatum, Lepidium sativum, or Sinapis alba seeds. Thus, amending agriculture soils with chlorhexidine containing sludge is unlikely to affect the germination of plants.

The effectiveness of a "EspaiJove.net"- a school-based intervention programme in increasing mental health knowledge, help seeking and reducing stigma attitudes in the adolescent population: a cluster randomised controlled trial.

BACKGROUND: The aim of this study is to evaluate the short- and long-term effects of the universal mental health literacy intervention "EspaiJove.net" in increasing mental health knowledge, help seeking and reducing stigma attitudes in the adolescent population. We also examine whether these effects depend on the intervention intensity.  METHODS: A clustered school-based randomised controlled trial (cRCT) design. SUBJECTS: 1,298 secondary pupils aged 13 and 14 were recruited from 18 schools in Barcelona (Spain) between September 2016 and January 2018. INTERVENTION: Three programmes were assessed: 1) Sensitivity Programme (SP; 1 h); 2) Mental Health Literacy (MHL; 6 h); 3) MHL plus a first-person Stigma Reduction Programme (MHL + SR; 7 h); 4) Control group (CG): waiting list. OUTCOME MEASURES: 1) MHL: EspaiJove.net EMHL Test (First part and Second Part); 2) Stigma: RIBS and CAMI; 3) Help-seeking and use of treatment: GHSQ. ANALYSIS: The data was collected at baseline, post-intervention and 6 and 12 months later. An intention-to-treat analysis and imputation method was used to analyse the missing data. Intervention effects were analysed using multilevel modelling. RESULTS: One thousand thirty-two students were included (SP = 225; MHL = 261; MHL + SR = 295 and CG = 251). The MHL and MHL + SR interventions showed short- and long-term an increase in knowledge compared to SP and CG, but no significant change post-intervention or over time (First part p = 0.52 and Second part p = 0.62) between intervention groups and CG. No significant changes were found in stigma scores post-intervention or over time (CAMI p = 0.61 and RIBS p = 0.98) or in help-seeking scores (parent p = 0.69; teacher p = 0.23 and healthcare professional p = 0.75). The MHL + SR intervention was the best valued and recommended (p < 0.005). CONCLUSIONS: The three interventions of the EspaiJove.net programme (SP, MHL and MHL + SR) seem not to be effective in terms MHL, Stigma and help-seeking behaviours. The contact with a person who has experimented mental illness first-hand did not reduce stigma attitudes. Further research should deal with the heterogeneity of MHL interventions (concept, duration and measures) and identify which components of stigma interventions are effective. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03215654 (registration date 12 July 2017).

A Preliminary Direct Comparison of the Inflammatory Reduction and Growth Factor Production Capabilities of Three Commercially Available Wound Products: Collagen Sheet, Manuka Honey Sheet, and a Novel Bioengineered Collagen Derivative + Manuka Honey + Hydroxyapatite Sheet.

Many commercially available wound products focus on improving one stage of the wound healing cascade. While this targeted approach works for specific wounds, there is a need for products that can reliably and comprehensively progress a wound through multiple stages. This preliminary in vitro study was performed to directly compare the inflammatory reduction and growth factor production effects of three commercially available wound care products: a collagen sheet (COL), a Manuka Honey Calcium Alginate sheet (MH), and a novel bioengineered sheet comprised of a collagen derivative (gelatin), Manuka honey, and hydroxyapatite (BCMH). Macrophages and human dermal fibroblasts were directly seeded on all three commercial products, and supernatants were analyzed for inflammatory markers and growth factors, respectively. Comparing the MMP-9/TIMP-1 ratio, BCMH resulted in 11× lower levels of this inflammation biomarker compared to COL, and 3× lower levels compared to MH. Both the COL and BCMH products created an environment conducive to expression and release of relevant growth factors, while the MH product showed the lowest levels of growth factor expression of all three commercially available products tested. The favorable 11× lower MMP-9/TIMP-1 ratio observed with the BCMH product compared to the COL product suggests that the BCMH products provided a superior comprehensive approach to healthy progression of the wounds by providing an additional benefit of reducing the inflammatory response in vitro.

Amoebic liver abscess in a COVID-19 patient: a case report.

BACKGROUND: Amoebiasis is a parasitic disease caused by Entamoeba histolytica, which affects people living in low- and middle-income countries and has intestinal and extraintestinal manifestations. To date, knowledge on coronavirus disease 2019 (COVID-19) coinfection with enteric parasites is limited, and E. histolytica coinfection has not been previously described. Here we present the case of a patient with COVID-19 who, during hospitalisation, presented a clinical picture consistent with an amoebic liver abscess (ALA). CASE PRESENTATION: A 54-year-old man, admitted as a suspected case of COVID-19, presented to our hospital with dyspnoea, malaise, fever and hypoxaemia. A nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction. After 7 days, he developed diarrhoea, choluria and dysentery. An abdominal ultrasound showed a lesion compatible with a liver abscess; stool examination revealed E. histolytica trophozoites, and additional serology for E. histolytica was positive. After 12 days of treatment with metronidazole, ceftazidime and nitazoxanide, the patient reported acute abdominal pain, and an ultrasound examination revealed free liquid in the abdominal cavity. An emergency exploratory laparotomy was performed, finding 3000 mL of a thick fluid described as "anchovy paste". Computed tomography scan revealed a second abscess. He ended up receiving 21 days of antibiotic treatment and was discharged with satisfactory improvement. CONCLUSION: Here we present, to the best of our knowledge, the first report of ALA and COVID-19 co-presenting. Based on their pathophysiological similarities, coinfection with SARS-CoV-2 and E. histolytica could change the patient's clinical course; however, larger studies are needed to fully understand the interaction between these pathogens.

Differences in Psychosocial Factors and Experimental Pain Sensitivity Between Hispanics and Non-Hispanic Whites from the U.S.-Mexico Border.

PURPOSE: Research suggests that ethnicity is a predictor of pain-related outcomes; however, studies comparing the differences in experimental pain sensitivity between Hispanics and non-Hispanic Whites (NHW) are scarce. This study investigated these differences between Hispanics and NHW from the U.S.- Mexico border. METHODS: Fifty-eight healthy participants completed the survey packet, which included a demographic and a psychosocial factors questionnaire. Participants underwent quantitative sensory testing, which included heat pain threshold, heat pain tolerance, Suprathreshold Heat Pain Response (SHPR), and Conditioned Pain Modulation (CPM). SHPR was induced by repeated thermal stimuli in both thenar eminences. CPM was assessed using SHPR as the experimental stimulus and cold pressor task as the conditioning stimulus. RESULTS: Analyses showed significant differences in experimental pain measures believed to be representative of facilitatory pain processing including SHPR and heat pain threshold, where Hispanics reported significantly higher pain ratings than NHW. Hispanics also reported higher levels of ethnic identity and acculturation. However, these factors were not significantly associated with experimental pain sensitivity. CONCLUSION: The experimental pain sensitivity and psychosocial factors included in this study differed by ethnic group, where Hispanics reported significantly higher pain ratings, when compared with NHW. However, ethnic identity and acculturation were not associated with these pain-related outcomes. Overall, enhanced understanding by clinicians of pain sensitivity and disparities in the pain experience between ethnic groups allows for increased cultural sensitivity and can be used to optimize pain treatment on an individual-by-individual basis.

Determination of cardiovascular drugs in sewage sludge by matrix solid-phase dispersion and ultra-performance liquid chromatography tandem mass spectrometry.

The current study presents a single step sample preparation procedure for the simultaneous determination of five antihypertensive (propranolol, losartan, irbesartan, telmisartan, and valsartan), three antiarrhythmic drugs (flecainide, dronedarone, and amiodarone), and one of their metabolites (N-desethylamiodarone) in sludge from municipal sewage treatment plants (STPs). Matrix solid-phase dispersion (MSPD) and ultra-performance liquid chromatography (UPLC) with tandem mass spectrometry (MS/MS) detection were selected as sample preparation and determination techniques, respectively. Under optimal conditions, MSPD extractions were carried out with freeze-dried samples (0.5 g) dispersed on 2 g of C18. Exhaustive extraction of target compounds was achieved with 10 mL of a methanol/acetonitrile/formic acid (30:69:1) solution. The obtained extract was ready for UPLC-MS/MS analysis without any further treatment, except filtration. The overall recoveries of the method (calculated against solvent-based standards) varied from 82 to 124%, with standard deviations in the range from 2 to 16%. Thus, the method was free of matrix effects during electrospray ionization. The achieved limits of quantification stayed between 2 and 10 ng g-1, and the linear response range extended to 5000 ng g-1. The occurrence of target compounds was investigated in sludge from 14 different STPs. High detection frequencies were observed for all compounds, with average concentrations above 100 ng g-1 for six cardiovascular drugs.

Multianalyte, high-throughput liquid chromatography tandem mass spectrometry method for the sensitive determination of fungicides and insecticides in wine.

Evidence of pesticide transfer from grapes to wine, added to differences in the national regulations regarding the number and the maximum concentration of these species in wine, demands analytical procedures suitable for their routine control in this foodstuff. In this research, solid-phase extraction (SPE) and ultra-performance liquid chromatography (UPLC), with tandem mass spectrometry (MS/MS) detection, are combined to obtain a sensitive and rapid procedure to determine 50 pesticides in red and white wines. Efficiency and selectivity of sample preparation are correlated with the type of sorbent, the elution solvent, and the physicochemical properties of pesticides. SPE of 2-mL wine samples followed by direct injection of the extract in the UPLC-MS/MS system provides quantification limits (LOQs) below 1 ng mL-1 for 48 out of 50 compounds, linear responses up to 200 ng mL-1, and acceptable accuracy, employing quantification against solvent-based standards, for 45 species. A total analysis time of 10 min, including compounds separation and re-equilibration of the UPLC column, was achieved. The developed methodology was applied to 25 wines (20 conventional and 5 ecological), produced in 7 different countries. Out of 27 pesticides quantified in these wines, 12 displayed occurrence frequencies above 24%; moreover, all wines, except one of the ecological ones, contained residues from at least one pesticide.

Assessment of quinoxyfen phototransformation pathways by liquid chromatography coupled to accurate mass spectrometry.

Quinoxyfen has been recently identified as a priority hazardous substance in the field of the European water policy. In this work, its fate in aqueous samples and solid supports under UV and solar radiation is investigated. Diverse degradation experiments were carried out, at lab scale, using spiked aliquots of different aqueous matrices (ultrapure, treated wastewater and river water) irradiated at different wavelengths (λ = 254 nm, λ = 365 nm and solar light). Half-lives of quinoxyfen (2-26 min) depended on the wavelength and the intensity of radiation whilst the nature of the aqueous matrix did not play an important role in degradation kinetics. Moreover, experiments under solar radiation of doped silicone tubes were performed to simulate degradation when quinoxyfen is adsorbed on plant leaves or soil. As the compound is not completely mineralized, the identification of quinoxyfen transformation products (TPs) was performed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) injection of different irradiated time aliquots. The full-fragment ion spectra, at different collision energies, allowed the elucidation of the chemical structure of TPs formed by hydroxylation, cyclization or cleavage reactions. Five out of seven identified TPs have not been reported previously. The ecotoxicity simulation by software (TEST and ECOSAR) for TPs revealed that some of them could cause harmful effects to organisms such as Daphnia magna or Fathead minnow in a similar extent to the precursor; moreover, the time course profiles of major TPs (TP1 and TP2) revealed a much higher resistance to further photodegradation than quinoxyfen. Graphical abstract Quinoxyfen phototransformation pathways.

Evaluation of nitrate effects in the photodegradability of cyprodinil. Kinetics study and transformation products elucidation.

The effects of nitrate in the kinetics and the transformation routes of the fungicide cyprodinil (CYP) were investigated using aqueous solutions, ultrapure water and river water samples, spiked with the precursor compound and containing different levels of nitrate. Samples were exposed either to 254 nm radiation or to solar light, depending on the experiment. Time course of CYP and formation of transformation products (TPs) were simultaneously assessed by direct injection of different irradiation time aliquots in a liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) system. Empirical formulae and structures of TPs were inferred from their accurate MS and MS/MS scan spectra, respectively. Under all investigated situations, nitrate anions enhanced the degradability of CYP with a noticeable reduction of its half-life (t 1/2). TPs arising from aqueous photodegradation of CYP were formed through three different routes: (1) hydroxylation of the benzenic ring; (2) hydroxylation of the pyrimidine cycle, followed by ring opening and further dealkylation; and (3) nitration of the benzenic ring. The latter group of TPs display higher estimated acute toxicities than CYP and remained stable for long irradiation times. Graphical Abstract Photonitration of cyprodinil.

Selective extraction of antimycotic drugs from sludge samples using matrix solid-phase dispersion followed by on-line clean-up.

An effective and selective, modular sample preparation method for the extraction of eight antimycotic drugs, belonging to three different chemical classes, from digested sludge samples is proposed. To this end, matrix solid-phase dispersion (MSPD) was on-line connected with a cationic exchanger solid-phase extraction (SPE) cartridge. Analytes were extracted from the MSPD syringe, which contained the freeze-dried sludge sample dispersed with C18 plus a clean-up layer of primary and secondary amine (PSA) sorbent, with 10 mL of methanol. This extract flowed also through the SPE cartridge, where target compounds remained trapped while neutral interferences are released. After discarding the MSPD syringe, analytes were recovered with 10 mL of methanol (0.5% in NH3) before LC-MS/MS determination using a hybrid quadrupole time-of-flight (QTOF) mass spectrometer furnished with an electrospray ionization (ESI) source. In comparison with previously published sample preparation methodologies, the developed approach greatly simplifies sample handling and reduces attenuation of ESI ionization for sample extracts when compared to standard solutions. The obtained absolute recoveries ranged between 70 and 118%, and the limits of quantification (LOQs) of the method varied between 5 and 8 ng g(-1). Four antimycotic drugs were ubiquitous in urban sludge samples, with maximum average concentrations (above 400 ng g(-1)) corresponding to clotrimazole (CTZ). The screening capabilities of the LC-QTOF-MS system demonstrated that the developed modular extraction and purification methodology might be useful for the selective extraction of other basic drugs (e.g., sertraline, amitryptiline, and amiodarone) from sludge.

Time-of-flight accurate mass spectrometry identification of quinoline alkaloids in honey.

Time-of-flight accurate mass spectrometry (TOF-MS), following a previous chromatographic (gas or liquid chromatography) separation step, is applied to the identification and structural elucidation of quinoline-like alkaloids in honey. Both electron ionization (EI) MS and positive electrospray (ESI+) MS spectra afforded the molecular ions (M(.+) and M+H(+), respectively) of target compounds with mass errors below 5 mDa. Scan EI-MS and product ion scan ESI-MS/MS spectra permitted confirmation of the existence of a quinoline ring in the structures of the candidate compounds. Also, the observed fragmentation patterns were useful to discriminate between quinoline derivatives having the same empirical formula but different functionalities, such as aldoximes and amides. In the particular case of phenylquinolines, ESI-MS/MS spectra provided valuable clues regarding the position of the phenyl moiety attached to the quinoline ring. The aforementioned spectral information, combined with retention times matching, led to the identification of quinoline and five quinoline derivatives, substituted at carbon number 4, in honey samples. An isomer of phenyquinoline was also noticed; however, its exact structure could not be established. Liquid-liquid microextraction and gas chromatography (GC) TOF-MS were applied to the screening of the aforementioned compounds in a total of 62 honeys. Species displaying higher occurrence frequencies were 4-quinolinecarbonitrile, 4-quinolinecarboxaldehyde, 4-quinolinealdoxime, and the phenylquinoline isomer. The Pearson test revealed strong correlations among the first three compounds.

Lipidomic analysis of polyunsaturated fatty acids and their oxygenated metabolites in plasma by solid-phase extraction followed by LC-MS.

The present work describes the development of a robust and sensitive targeted analysis platform for the simultaneous quantification in blood plasma of lipid oxygenated mediators and fatty acids using solid-phase extraction (SPE) and high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The concurrent analysis of these lipid mediators is challenging because of their instability, differences in solubility, and the frequent occurrence of isobaric forms with similar fragmentation patterns. Results demonstrated that the reduction of SPE temperature to 4 °C is a critical parameter for preserving the hydroperoxy derivatives. Polymeric HLB cartridges increased 40-50 % ARA, EPA, and DHA sensitivity compared to C18 sorbent and also provided higher global performance for most hydroxides and other oxidation products. The proposed method for the two tested mass analyzers yields high sensitivity, good linearity, and reproducibility, with detection limits ranging 0.002-7 ng/mL and global recoveries as high as 85-112 %. However, the additional advantage of the linear ion trap (LIT) mass analyzer working in full scan product ion mode, compared to the triple quadrupole (QqQ) operating in multiple reaction monitoring (MRM), should be noted: the full scan product ion mode provides the full fragmentation spectra of compounds that allowed the discrimination of coeluting isomers and false positive identifications without additional chromatography development. The proposed lipidomic procedure demonstrates a confident, simple, and sensitive method to profile in plasma a wide range of lipid eicosanoid and docosanoid mediators, including innovatively the analysis of hydroperoxy congeners and nonoxidized PUFA precursors.

Comprehensive analysis of vitamin D3 impurities in oily drug products using supercritical fluid chromatography-mass spectrometry.

Vitamin D3, an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D3 in oily drug products using supercritical fluid chromatography-mass spectrometry (SFC-MS). Targeted impurities include two esters of vitamin D3 and five non-esters including four that are isobaric to vitamin D3. Firstly, a screening study highlighted the Torus 1-AA column and acetonitrile modifier as adequate for the separation, followed by optimization of the SFC conditions. Secondly, make-up solvent composition and MS settings were optimized to reach high sensitivity. For both the separation and MS response, the screening design of experiments proved useful. Lastly, a fast saponification and liquid-liquid extraction method was developed, enabling efficient sample cleanup and impurities recovery from the complex oily matrix. The SFC-MS method suitability was assessed in two validation studies. The first study employed the ICH Q2 guideline for impurity limit test to demonstrate method specificity and establish a limit of detection (LOD) and a limit of quantification (LOQ) at 0.2% and 0.5%, respectively, for ester impurities. The second study conducted a comprehensive quantitative assessment for three non-ester impurities using a total error approach, determining method validity through accuracy profiles. The validated method exhibited reliable performance across impurity concentrations from 0.1% to 2.0%, with estimated LODs ranging from 2 to 7 ng/mL. This study further promotes SFC-MS as a valuable, versatile, and green tool for routine pharmaceutical QC.

Do Longer Fins Improve Ocean Rescues? A Comprehensive Investigation into Lifeguard Performance and Physiological Impact.

Coastal environments present dynamic challenges necessitating rapid and efficient responses during aquatic emergencies. Lifeguards, as pivotal links in the intervention chain, rely on various tools, with rescue time being paramount. The choice of fins, specifically long versus short ones, plays a critical role in optimizing lifeguard performance during rescues. This randomized cross-over study explores the impact of flipper size on ocean rescues, employing a sample of 14 lifeguards. Long fins (LFs) and short fins (SFs) were compared in terms of rescue time (RT) and physiological load (PL). Tests included ocean rescues without fins (R), with LF (R-LF), and with SF (R-SF). Variables recorded encompassed swim approach time, tow-in time, overall rescue time, perceived exertion rates (RPEs), and post-rescue lactate concentration. Long fins demonstrated superior performance in swim approach and tow-in times compared to both short fins and no fins (p < 0.001). Overall rescue time favored long fins significantly (p < 0.001), indicating their efficiency in practical ocean rescue scenarios. Physiologically, long fins induced lower perceived exertion in arms (p = 0.033) compared to short fins. Lactate concentrations post-rescue revealed no significant differences (p > 0.05). This study demonstrates that long fins significantly improve lifeguard performance during ocean rescues, reducing rescue times and alleviating arm fatigue.

Physicochemical Properties and Microbiome of Vineyard Soils from DOP Ribeiro (NW Spain) Are Influenced by Agricultural Management.

Agricultural management influences the soil ecosystem by affecting its physicochemical properties, residues of pesticides and microbiome. As vineyards grow crops with the highest incidence of pesticides, the aim of this study was to evaluate the impact of conventional and sustainable management systems of vineyards from DOP Ribeiro on the soil's condition. Samples from soils under three different management systems were collected, and the main soil physicochemical properties were evaluated. A selection of 50 pesticides were investigated by liquid chromatography with tandem mass spectrometry. The bacterial and fungal microbiomes were characterized through amplicon sequencing. The results show that organic agriculture positively influences soil pH and the concentration of some nutrients compared to conventional management. Our microbiome analysis demonstrated that transitioning from conventional to organic management significantly improves several BeCrop® indexes related to key microbial metabolism and soil bio-sustainability. Such a transition does not affect soil alpha diversity, but leads to a higher interconnected microbial network structure. Moreover, differential core genera and species for each management system are observed. In addition, the correlation of the microbiome with geographical distance is evidence of the existence of different microbial terroirs within DOP Ribeiro. Indeed, sustainable management leads to higher nutrient availability and enhances soil health in the short term, while lowering pesticide usage.

[Mental health literacy in spanish adolescents and its relationship with sociodemographic characteristics]. / Alfabetización en salud mental en adolescentes españoles y su relación con las características sociodemográficas.

OBJECTIVE: Different studies identify mental health literacy as a protective factor for developing a mental health problem. The aim of this paper was to determine the degree of mental health literacy of the adolescent population of Barcelona, and its relationship with socio-demographic and educational variables. METHODS: A cross-sectional study was carried out in Barcelona during the 2017-2018 academic year. A total of 1,032 young people between thirteen and seventeen years of age participated. The following variables were collected: sex, age, nationality, socioeconomic status (RDHpc) and average school grade. The aim was to determine the degree of mental health literacy (knowledge, stigma and help-seeking) of the adolescent population of Barcelona, and its relationship with socio-demographic and educational variables. Multiple linear regression analysis was performed adjusting for the effect of sociodemographic variables on the score of each scale. RESULTS: The mean score (standard deviation) of the EMHL test was 7.28 (1.27) and 4.24 (1.14) respectively, with higher scores obtained by girls, high RDHpc, excellent score and Spanish nationality. The greatest difference in EMHL scores, adjusting for the rest of the variables, corresponded to adolescents with an excellent mean score and a high RDHpc index (with respect to the baseline category, beta=0.72 and 0.52 respectively). The mean stigma score was 27.6 (4.47) for CAMI and 8.83 (3.36) for RIBS. The variables related to a greater difference in score with respect to the baseline category and adjusted for the rest of the variables were: gender (boy=1.54) and academic grade (excellent=-2.38) for CAMI, and nationality (foreign=0.82) and academic grade (excellent=-1.30) for RIBS. The mean RIBS score was 8.83 (3.36) with the largest difference in score from baseline being foreign nationality (beta=0.82) and having a grade of excellent (1.30). Help-seeking was higher in parents and friends, with differences according to gender and nationality. CONCLUSIONS: The level of mental health literacy is medium-low. While gender, nationality and educational attainment are the factors that are related to knowledge and stigma, socio-economic status is only related to mental health literacy.

OBJECTIVE: Diferentes estudios identifican la alfabetización en salud y/o salud mental (ASM) como factores protectores contra el desarrollo de un problema de salud mental. El objetivo de este trabajo fue determinar el grado de alfabetización en salud mental de la población adolescente de Barcelona, así como su relación con variables sociodemográficas y educativas. METHODS: Se realizó un estudio transversal en Barcelona durante el curso 2017-2018. Participaron 1.032 jóvenes entre trece y diecisiete años. Se recogieron las siguientes variables: sexo; edad; nacionalidad; nivel socioeconómico (RDHpc); y nota media escolar. La ASM se midió mediante los test de conocimientos EMHL (reconocimiento de problemas mentales y conocimientos en salud mental; rango 0-10 cada parte), estigma (CAMI: rango 10-50, y RIBS: rango 4-20) y búsqueda de ayuda (GHSQ: rango de 1 a 7). Se realizó análisis de regresión lineal múltiple ajustando el efecto de variables sociodemográficas sobre la puntuación de cada escala. RESULTS: La puntuación media (desviación típica) del EMHL test fue de 7,28 (1,27) y 4,24 (1,14), respectivamente, obteniendo mayor puntuación las chicas, RDHpc altas, nota excelente y con nacionalidad española. La mayor diferencia de puntuación en EMHL, ajustando por el resto de variables, correspondió a los adolescentes con nota media excelente y con índice RDHpc elevado (respecto a la categoría basal, beta=0,72 y 0,52, respectivamente). La puntuación media del estigma fue 27,6 (4,47) para CAMI y 8,83 (3,36) para RIBS. Las variables relacionadas con una mayor diferencia de puntuación respecto a la categoría basal y ajustado por el resto de variables fueron: sexo (chico=1,54) y nota académica (excelente=-2,38) para CAMI, y nacionalidad (extranjera=0,82) y nota académica (excelente=-1,30) para RIBS. La puntuación media de RIBS fue 8,83 (3,36), siendo la mayor diferencia de puntuación respecto a la categoría basal la nacionalidad extranjera (beta=0,82) y tener una nota de excelente (1,30). La búsqueda de ayuda fue mayor en padres/madres y amigos, con diferencias según sexo y nacionalidad. CONCLUSIONS: El nivel de alfabetización de salud mental es medio-bajo. Mientras que género, nacionalidad y resultados académicos son los factores que se relacionan con conocimientos y estigma, el nivel socioeconómico se relaciona únicamente con conocimientos en salud mental.