ABSTRACT
Ciguateric syndrome is a food poisoning associated with the consumption of some species of fish that have accumulated ciguatoxins (CTXs) in their tissues. The effects of the syndrome occur with nervous imbalances which have been described for quite some time, and mentioned in sailing literature for centuries. In the last decade, research has been focused on the implementation of analytical methods for toxin identification and the study of action modes of CTXs to design effective treatments. However, an important aspect is to determine the damage that CTXs caused in the organs of affected individuals. In this work, the damages observed in tissues of mice, mainly in the small intestine, were analyzed. The animals were fed with CTX-contaminated fish muscle at concentrations 10-times below the median lethal dose (LD50) for 10 weeks. The analysis of tissues derived from the oral treatment resulted in an increased occurrence of Paneth cells, presence of lymphoid tissue infiltrating the mucosa and fibrous lesions in the mucosal layer of the small intestine. A decreasing weight in animals fed with toxic muscle was observed.
Subject(s)
Ciguatoxins , Fishes , Intestine, Small , Animals , Intestine, Small/drug effects , Intestine, Small/pathology , Ciguatoxins/toxicity , Mice , Food Contamination/analysis , Ciguatera Poisoning , Male , Seafood , Lethal Dose 50ABSTRACT
INTRODUCTION: Our aim was to investigate the prevalence of atrial fibrillation (AF) and recently diagnosed lung cancer in the outpatient oncology clinic and to describe the clinical profile, management and outcomes of this population. METHODS: Among 6984 patients visited at the outpatient oncology clinics attending lung cancer patients in five university hospitals from 2017 to 2019, all consecutive subjects with recently diagnosed (<1 year) disease and AF were retrospectively selected and events in follow up were registered. RESULTS: A total of 269 patients (3.9 % of all attended, 71 ± 8 years, 91 % male) were included. Charlson, CHA2DS2-VASc and HAS-BLED indexes were 6.7 ± 2.9, 2.9 ± 1.5 y 2.5 ± 1.2, respectively. Tumour stage was I, II, III and IV in 11 %, 11 %, 33 % and 45 % of them, respectively. Anticoagulants were prescribed to 226 patients (84 %): direct anticoagulants (n = 99;44 %), low molecular weight heparins (n = 69;30 %) and vitamin K antagonists (n = 58;26 %). After 46 months of maximum follow-up, 186 patients died (69 %). Cumulative incidences of events at 3 years were 3.3 ± 1.3 % for stroke/systemic embolism (n = 7); 8.9 ± 2.2 % for thrombotic events (n = 18); 9.9 ± 2.6 % for major bleeding (n = 16), and 15.9 ± 3,0 % for cardiovascular events (n = 33). In patients with early stages of cancer (I-II), 2-year mortality was significantly higher in those with cardiovascular events or major bleeding (85 % vs 25 %, p = 0.01). CONCLUSION: Nearly 4 % or all outpatients in the oncology clinic attending lung cancer present recently diagnosed disease and AF. Major bleeding and cardiovascular event rates are high in this population, with an impact on mortality in early stages of cancer.
Subject(s)
Atrial Fibrillation , Lung Neoplasms , Stroke , Humans , Male , Female , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Outpatients , Retrospective Studies , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/chemically induced , Hemorrhage/chemically induced , Stroke/epidemiology , Anticoagulants/therapeutic use , Risk Factors , Risk AssessmentABSTRACT
The utilization of host-cell machinery during SARS-CoV-2 infection can overwhelm the protein-folding capacity of the endoplasmic reticulum and activate the unfolded protein response (UPR). The IRE1α-XBP1 arm of the UPR could also be activated by viral RNA via Toll-like receptors. Based on these premises, a study to gain insight into the pathogenesis of COVID-19 disease was conducted using nasopharyngeal exudates and bronchioloalveolar aspirates. The presence of the mRNA of spliced XBP1 and a high expression of cytokine mRNAs were observed during active infection. TLR8 mRNA showed an overwhelming expression in comparison with TLR7 mRNA in bronchioloalveolar aspirates of COVID-19 patients, thus suggesting the presence of monocytes and monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a synthetic mimic of SARS-CoV-2 RNA, showed induction of XBP1 splicing and the expression of proinflammatory cytokines. These responses were blunted by the IRE1α inhibitor MKC8866, the TLR8 antagonist CU-CPT9a, and knockdown of TLR8 receptor. In contrast, the IRE1α-XBP1 activator IXA4 enhanced these responses. Based on these findings, the TLR8/IRE1α system seems to play a significant role in the induction of the proinflammatory cytokines associated with severe COVID-19 disease and might be a druggable target to control cytokine storm.
Subject(s)
COVID-19 , Endoribonucleases , Humans , Cytokines , Endoribonucleases/genetics , Endoribonucleases/metabolism , Lung/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , RNA, Viral , SARS-CoV-2/genetics , Toll-Like Receptor 8/genetics , X-Box Binding Protein 1/genetics , X-Box Binding Protein 1/metabolismABSTRACT
Squalene-derived polyethers are a unique class of compounds that display a great diversity of structures and a broad array of bioactivities, among which its notable antiproliferative activity stands out against various types of cancer cell lines. In this study, eighteen triterpene squalene-derived polyethers, including twelve natural products and six synthetic derivatives, obtained from the red alga Laurencia viridis Gil-Rodríguez & Haroun were screened for their antiproliferative activity against six cancer cell lines: A549, HBL-100, HeLa, SW1573, T-47D, and WiDr; and a structure-activity relationship (SAR) study was established.
ABSTRACT
The genus Ganoderma has a long history of use in traditional Asiatic medicine due to its different nutritional and medicinal properties. In Mexico, the species G. tuberculosum is used in indigenous communities, for example, the Wixaritari and mestizos of Villa Guerrero Jalisco for the treatment of diseases that may be related to parasitic infections; however, few chemical studies corroborate its traditional medicinal potential. Thereby, the objective of this study was to isolate and identify anti-parasitic activity compounds from a strain of G. tuberculosum native to Mexico. From the fruiting bodies of G. tuberculosum (GVL-21) a hexane extract was obtained which was subjected to guided fractioning to isolate pure compounds. The in vitro anti-parasitic activity of the pure compound (IC50) was assayed against Leishmania amazonensis, Trypanosoma cruzi, Acanthamoeba castellanii Neff, and Naegleria fowleri. Furthermore, the cytotoxicity (CC50) of the isolated compounds was determined against murine macrophages. The guided fractioning produced 5 compounds: ergosterol (1), ergosta-4,6,8(14),22-tetraen-3-one (2), ergosta-7,22-dien-3ß-ol (3), 3,5-dihydroxy-ergosta-7,22-dien-6-one (4), and ganoderic acid DM (5). Compounds 2 and 5 showed the best anti-parasitic activity in an IC50 range of 54.34 ± 8.02 to 12.38 ± 2.72 µM against all the parasites assayed and low cytotoxicity against murine macrophages. The present study showed for the first time the in vitro anti-parasitic activity of compounds 1-5 against L. amazonensis, T. cruzi, A. castellanii Neff, and N. fowleri, corroborating the medicinal potential of Ganoderma and its traditional applications.
Subject(s)
Anti-Infective Agents , Ganoderma , Animals , Mice , Antiparasitic Agents , Mexico , Ganoderma/chemistryABSTRACT
Naegleria fowleri is the causative agent of a central nervous system affecting disease called primary amoebic meningoencephalitis. It is a fulminant disease with a rapid progression that affects mainly children and young adults who report previous water exposure. Current treatment options are not totally effective and involve several side effects. In this work, six meroterpenoids isolated from the brown algae Gongolaria abies-marina were evaluated against N. fowleri. Gongolarone B (1), 6Z-1'-methoxyamentadione (2), and 1'-methoxyamentadione (3) were the most active molecules against N. fowleri with IC50 values between 13.27 ± 0.96 µM and 21.92 ± 1.60 µM. However, cystomexicone B (6) was the molecule with the highest selectivity index (>8.5). Moreover, all these compounds induced different cellular events compatible with the apoptosis-like PCD process, such as chromatin condensation, damages at the mitochondrial level, cell membrane disruption, and production of reactive oxygen species (ROS). Therefore, G. abies-marina could be considered as a promising source of active molecules to treat the N. fowleri infections.
ABSTRACT
Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus Leishmania, triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga Laurencia johnstonii have been studied for this purpose. The different compounds were tested in vitro against the promastigote and amastigote forms of Leishmania amazonensis. Different assays were also performed, including the measurement of mitochondrial potential, determination of ROS accumulation, and chromatin condensation, among others, focused on the detection of the cell death process known in this type of organism as apoptosis-like. Five compounds were identified that displayed leishmanicidal activity: laurequinone, laurinterol, debromolaurinterol, isolaurinterol, and aplysin, showing IC50 values against promastigotes of 1.87, 34.45, 12.48, 10.09, and 54.13 µM, respectively. Laurequinone was the most potent compound tested and was shown to be more effective than the reference drug miltefosine against promastigotes. Different death mechanism studies carried out showed that laurequinone appears to induce programmed cell death or apoptosis in the parasite studied. The obtained results underline the potential of this sesquiterpene as a novel anti-kinetoplastid therapeutic agent.
Subject(s)
Antiprotozoal Agents , Leishmania mexicana , Leishmania , Leishmaniasis , Humans , Animals , Mice , Leishmaniasis/drug therapy , Skin , Plant Extracts/pharmacology , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Mice, Inbred BALB CABSTRACT
Naegleria fowleri is an opportunistic protozoan, belonging to the free-living amoeba group, that can be found in warm water bodies. It is causative agent the primary amoebic meningoencephalitis, a fulminant disease with a rapid progression that affects the central nervous system. However, no 100% effective treatments are available and those that are currently used involve the appearance of severe side effects, therefore, there is an urgent need to find novel antiamoebic compounds with low toxicity. In this study, the in vitro activity of six oxasqualenoids obtained from the red algae Laurencia viridis was evaluated against two different strains of N. fowleri (ATCC® 30808 and ATCC® 30215) as well as their cytotoxicity against murine macrophages. Yucatecone was the molecule with the highest selectivity index (>2.98 and 5.23 respectively) and it was selected to continue with the cell death type determination assays. Results showed that yucatone induced programmed cell death like responses in treated amoebae causing DNA condensation and cellular membrane damage among others. In this family of oxasqualenoids, it seems that the most significative structural feature to induce activity against N. fowleri is the presence of a ketone at C-18. This punctual oxidation transforms an inactive compound into a lead compound as the yucatecone and 18-ketodehydrotyrsiferol with IC50 values of 16.25 and 12.70 µM, respectively. The assessment of in silico ADME/Tox analysis revealed that the active compounds showed good Human Oral Absorption and demonstrate that are found to be within the limit of approved drug parameter range. Hence, the study highlights promising potential of yucatone to be tested for therapeutic use against primary amoebic meningoencephalitis.
Subject(s)
Amoeba , Central Nervous System Protozoal Infections , Naegleria fowleri , Humans , Animals , Mice , Central Nervous System Protozoal Infections/drug therapyABSTRACT
Packed-bed biofilm photobioreactor combined with ultrafiltration membrane was investigated for intensifying the process for secondary wastewater effluent treatment. Cylindrical glass carriers were used as supporting material for the microalgal-bacterial biofilm, which developed from indigenous microbial consortium. Glass carriers allowed adequate growth of the biofilm with limited suspended biomass. Stable operation was achieved after a start-up period of 1000 h, where supernatant biopolymer clusters were minimized and complete nitrification was observed. After that time, biomass productivity was 54 ± 18 mg·L-1·day-1. Green microalgae Tetradesmus obliquus and several strains of heterotrophic nitrification-aerobic denitrification bacteria and fungi were identified. Combined process exhibited COD, nitrogen and phosphorus removal rates of 56 ± 5%, 12 ± 2% and 20 ± 6%, respectively. Membrane fouling was mainly caused by biofilm formation, which was not effectively mitigated by air-scouring aided backwashing.
Subject(s)
Microalgae , Water Purification , Photobioreactors/microbiology , Wastewater , Ultrafiltration , Nitrification , Biofilms , Biomass , Nitrogen , Bioreactors , DenitrificationABSTRACT
Bioaccumulation is the process by which living organisms accumulate substances, such as pesticides, heavy metals, and other pollutants, from their environment. These substances can accumulate in the organism's tissues over time, leading to potential health risks. Bioaccumulation can occur in both aquatic and terrestrial ecosystems, and can have a significant impact on the health of both humans and wildlife. The objective of this study is to find out if the concentrations of metals in the tuna species of the Canary Islands are suitable for human consumption and if they pose a health risk. Fifteen samples of Acanthocybium solandri, Katsuwonus pelamis, Thunnus albacares, Thunnus obesus and Thunnus thynnus present in canaries were analyzed. Ten grams of muscle were taken from each specimen and the metals Al, Cd, Cr, Cu, Fe, Li, Ni, Pb and Zn were determined by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The tuna species that presented more metals with a higher concentration compared to the others was T. thynnus, reaching up to 100 times more than the other studied species in Fe content with 137.8 ± 100.9 mg/Kg, which may be due to the fact that it is the largest species that reaches ages of more than fifteen years. The species Thunnus thynnus should not be suitable for commercialization according to the current legislation on the concentrations of Cd in blue fish, since 75% of the specimens studied exceeded the concentration legislated for Cd. A total of 40% of the studied specimens of this this species exceeded the legislated values for the concentration of Pb in oily fish meat, so this species must be monitored to ensure that it does not pose a risk to human health.
ABSTRACT
Leishmaniasis and Chagas disease affect millions of people worldwide. The available treatments against these parasitic diseases are limited and display multiple undesired effects. The brown alga belonging to the genus Gongolaria has been previously reported as a source of compounds with different biological activities. In a recent study from our group, Gongolaria abies-marine was proven to present antiamebic activity. Hence, this brown alga could be a promising source of interesting molecules for the development of new antiprotozoal drugs. In this study, four meroterpenoids were isolated and purified from a dichloromethane/ethyl acetate crude extract through a bioguided fractionation process targeting kinetoplastids. Moreover, the in vitro activity and toxicity were evaluated, and the induction of programmed cell death was checked in the most active and less toxic compounds, namely gongolarone B (2), 6Z-1'-methoxyamentadione (3) and 1'-methoxyamentadione (4). These meroterpenoids triggered mitochondrial malfunction, oxidative stress, chromatin condensation and alterations of the tubulin network. Furthermore, a transmission electron microscopy (TEM) image analysis showed that meroterpenoids (2-4) induced the formation of autophagy vacuoles and ER and Golgi complex disorganization. The obtained results demonstrated that the mechanisms of action at the cellular level of these compounds were able to induce autophagy as well as an apoptosis-like process in the treated parasites.
ABSTRACT
Naegleria fowleri is an opportunistic protozoon that can be found in warm water bodies. It is the causative agent of the primary amoebic meningoencephalitis. Focused on our interest to develop promising lead structures for the development of antiparasitic agents, this study was aimed at identifying new anti-Naegleria marine natural products from a collection of chamigrane-type sesquiterpenes with structural variety in the levels of saturation, halogenation and oxygenation isolated from Laurencia dendroidea. (+)-Elatol (1) was the most active compound against Naegleria fowleri trophozoites with IC50 values of 1.08 µM against the ATCC 30808™ strain and 1.14 µM against the ATCC 30215™ strain. Furthermore, the activity of (+)-elatol (1) against the resistant stage of N. fowleri was also assessed, showing great cysticidal properties with a very similar IC50 value (1.14 µM) to the one obtained for the trophozoite stage. Moreover, at low concentrations (+)-elatol (1) showed no toxic effect towards murine macrophages and could induce the appearance of different cellular events related to the programmed cell death, such as an increase of the plasma membrane permeability, reactive oxygen species overproduction, mitochondrial malfunction or chromatin condensation. Its enantiomer (-)-elatol (2) was shown to be 34-fold less potent with an IC50 of 36.77 µM and 38.03 µM. An analysis of the structure-activity relationship suggests that dehalogenation leads to a significant decrease of activity. The lipophilic character of these compounds is an essential property to cross the blood-brain barrier, therefore they represent interesting chemical scaffolds to develop new drugs.
Subject(s)
Laurencia , Naegleria fowleri , Sesquiterpenes , Spiro Compounds , Animals , Mice , Laurencia/chemistry , Spiro Compounds/pharmacology , Sesquiterpenes/pharmacologyABSTRACT
Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1'-methoxyamentadione (5) and 6Z-1'-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba.
Subject(s)
Acanthamoeba castellanii , Amebicides , Animals , Humans , Amebicides/pharmacology , Trophozoites , Actin CytoskeletonABSTRACT
The City Region Food Systems approach has been proposed to achieve food system resilience and nutrition security while promoting the urgent ecological transition within urban and peri-urban areas, especially after the COVID-19 pandemic. However, the great diversity of the initiatives composing City Region Food Systems in Europe poses barriers to the assessment of their integrated sustainability. Hence, the present work is developed within the EU-H2020 project Food System in European Cities (FoodE), to build a consistent sustainability scoring system that allows comparative evaluation of City Region Food System Initiatives. Adopting a Life Cycle Thinking approach, it advances on existing knowledge and past projects, taking advantage of a participatory process, with stakeholders from multidisciplinary expertise. As a result, the research designs, and tests on 100 case studies a simplified and ready-to-use scoring mechanism based on a quali-quantitative appraisal survey tool, delivering a final sustainability score on a 1-5 points scale, to get insights on the social, economic, and environmental impacts. As in line with the needs of the UN Sustainable Development Goals, the outcome represents a step forward for the sustainable development and social innovation of food communities in cities and regions, providing a practical and empirical lens for improved planning and governance.
ABSTRACT
Background: Women and men with chronic coronary syndrome (CCS) have different clinical features and management, and studies on mid-term prognosis have reported conflicting results. Our objective was to investigate the impact of the female sex in the prognosis of the disease in the very long term. Methods and Results: We investigated differential features and very long-term prognosis in 1268 consecutive outpatients with CCS (337 [27%] women and 931 [73%] men). Women were older than men, more likely to have hypertension, diabetes, angina, and atrial fibrillation, and less likely to be exsmoker/active smoker and to have been treated with coronary revascularization (p < 0.05 for all). The prescription of statins, antiplatelets, and betablockers was similar in both groups. After up to 17 years of follow-up (median = 11 years, interquartile range = 4-15 years), cumulative incidences of acute myocardial infarction (10.2% vs. 11.8%) or stroke (11% vs. 10%) at median follow-up were similar, but the risks of major cardiovascular events (acute myocardial infarction, stroke, or cardiovascular death, 41.2% vs. 33.6%), hospital admission for heart failure (20.9% vs. 11.9%), or cardiovascular death (32.3% vs. 22.1%) were significantly higher for women (p < 0.0005), with a nonsignificant trend to higher overall mortality (45.2% vs. 39.1%, p = 0.07). However, after multivariate adjustment, all these differences disappeared. Conclusion: Although women and men with CCS presented a different clinical profile, and crude rates of major cardiovascular events, heart failure and cardiovascular death were higher in women, female sex was not an independent prognostic factor in this study with up to 17 years of follow-up.
Subject(s)
Heart Failure , Myocardial Infarction , Stroke , Male , Humans , Female , Prognosis , Prospective Studies , Risk Factors , Sex FactorsABSTRACT
Ciguatera poisoning (CP) is a foodborne disease known for centuries; however, little research has been conducted on the effects of ciguatoxins (CTXs) on fish metabolism. The main objective of this study was to assess different hepatic compounds observed in goldfish (Carassius auratus) fed C-CTX1 using nuclear magnetic resonance (NMR)-based metabolomics. Thirteen goldfish were treated with C-CTX1-enriched flesh and sampled on days 1, 8, 15, 29, 36, and 43. On day 43, two individuals, referred to as 'Detox', were isolated until days 102 and 121 to evaluate the possible recovery after returning to a commercial feed. At each sampling, hepatic tissue was weighed to calculate the hepatosomatic index (HSI) and analyzed for the metabolomics study; animals fed toxic flesh showed a higher HSI, even greater in the 'Detox' individuals. Furthermore, altered concentrations of alanine, lactate, taurine, glucose, and glycogen were observed in animals with the toxic diet. These disturbances could be related to an increase in ammonium ion (NH4+) production. An increase in ammonia (NH3) concentration in water was observed in the aquarium where the fish ingested toxic meat compared to the non-toxic aquarium. All these changes may be rationalized by the relationship between CTXs and the glucose-alanine cycle.
ABSTRACT
Dinoflagellate-derived polyketides are typically large molecules (>1000 Da) with complex structures, potent bioactivities, and high toxicities. Their discovery suffers three major bottlenecks: insufficient bioavailability, low-yield cultivation of producer organisms, and production of multiple highly related analogues by a single strain. Consequently, the biotechnological production of therapeutics or toxicological standards of dinoflagellate-derived polyketides is also hampered. Strategies based on sensitive and selective techniques for chemical prospection of dinoflagellate extracts could aid in overcoming these limitations, as it allows selecting the most interesting candidates for discovery and exploitation programs according to the biosynthetic potential. In this work, we assess the combination of data-dependent liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS2) and molecular networking to screen polyol polyketides. To demonstrate the power of this approach, we selected dinoflagellate Amphidinium carterae since it is commonly used as a biotechnological model and produces amphidinols, a family of polyol-polyene compounds with antifungal and antimycoplasmal activity. First, we screened families of compounds with multiple hydroxyl groups by examining MS2 profiles that contain sequential neutral losses of water. Then, we clustered MS2 spectra by molecular networking to facilitate the dereplication and discovery of amphidinols. Finally, we used the MS2 fragmentation behavior of well-characterized luteophanol D as a model to propose a structural hypothesis of nine novel amphidinols. We envision that this strategy is a valuable approach to rapidly monitoring toxin production of known and unknown polyol polyketides in dinoflagellates, even in small culture volumes, and distinguishing strains according to their toxin profiles.
Subject(s)
Dinoflagellida , Polyketides , Antifungal Agents/chemistry , Dinoflagellida/chemistry , Polyenes , Polyketides/chemistry , Polymers , WaterABSTRACT
Our aim was to investigate the role of left atrial longitudinal strain (LALS) in the non-invasive diagnosis of acute cellular rejection (ACR) episodes in heart transplant (HTx) recipients. Methods: We performed successive echocardiographic exams in 18 consecutive adult HTx recipients in their first year after HTx within 3 h of the routine surveillance endomyocardial biopsies (EMB) in a single center. LALS parameters were analyzed with two different software. We investigated LALS association with ACR presence, as well as inter-vendor variability in comparable LALS values. Results: A total of 147 pairs of EMB and echo exams were carried out. Lower values of LALS were significantly associated with any grade of ACR presence. Peak atrial longitudinal strain (PALS) offered the best diagnostic value for any grade of ACR, with a C statistic of 0.77 using one software (95% CI 0.68−0.84, p < 0.0005) and 0.64 with the other (95% CI 0.54−0.73, p = 0.013) (p = 0.02 for comparison between both curves). Reproducibility between comparable LALS parameters was poor (intraclass correlation coefficients were 0.60 for PALS, 95% CI 0.42−0.73, p < 0.0005; and 0.42 for PALS rate, 95% CI −0.13−0.68, p < 0.0005). Conclusions: LALS variables might be a sensitive marker of ACR in HTx recipients, principally discriminating between those studies without rejection and those with any grade of ACR. Inter-vendor variability was significant.
ABSTRACT
The present study evaluates the adverse effects of three vaccines: AstraZeneca (Vaxzevria), Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax) according to the dose. From 733 participants collected, the vaccine schedule was as follows: 330 (45%) received a double dose of the AstraZeneca vaccine, 382 (52.1%) received a double dose of Pfizer, 18 (2.5%) received a heterologous prime boost and 3 (0.4%) received a single dose. Pfizer and Moderna vaccines were administered as a third dose in 70 and 121 individuals, respectively. Local and systemic reactions observed in the three vaccines were mild to moderate in severity. Only one AstraZeneca recipient (0.3%) presented a serious adverse effect: blurred vision. Adverse events were more frequent after the first dose of AstraZeneca and after the second dose of Pfizer. As the third dose, Moderna causes more adverse effects than Pfizer regardless of the type of vaccine previously administered, whereas the reactogenicity of a third dose of Pfizer is slightly higher in the group previously vaccinated with Pfizer than in that group with AstraZeneca. In short, secondary effects of the third dose of COVID-19 vaccines were similar to those after dose 2, but their frequency depends on the type of vaccine and the combinations of vaccines.
ABSTRACT
Avocado consumption and trade are increasing worldwide, with North America and Europe being the main importing regions. Spain is the major European avocado producer (90% of the production), yet it only supplies 10% of the market. Consequently, more than 90% of the avocados consumed in Europe are imported from overseas, mainly from Chile and Peru. In this work, the Life Cycle Assessment (LCA) impact associated with the transport of two avocado supply chains (short (Spanish) and long (Chilean)) and the effect of the fruit origin and distance of both chains on primary and secondary metabolites from harvest to edible ripeness were evaluated using a gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to diode array detection (LC-DAD) based metabolite analysis. The LCA transport impact of the fresh supply chain from production centers in Chile (Quillota) and Spain (Malaga), and then the distribution to several cities in Europe, suggested road export from Spain to European capitals to have the lowest impact (0.14 to 0.22 kg CO2 eq/kg of avocado). When export from Chile was considered, the option of oceanic freight to European ports closer to final destinations was clearly a better option (0.21 to 0.26 kg CO2 eq/kg) than via the Algeciras port in Spain followed by road transport to final destinations in European capitals (0.34 to 0.43 kg CO2 eq/kg), although the situation could be somewhat different if the avocados are transported from the destination ports in northern Europe to long-distance capitals in other European countries. Fruit origin had a significant impact on avocado primary and secondary metabolites. The conditions of the supply chain itself (10 d in cold storage in regular conditions vs. 30 d cold storage + controlled atmosphere conditions) largely influence the fate of some metabolites that certainly affect the pool of metabolites at edible ripeness. The long-assumed hypothesis that the longer the supply chain the more negative impact on nutritional and functional compounds might not hold in this case, as long as transport conditions are adequate in terms of temperature, atmosphere conditions, and time considering distance from origin to destination.