First Record of Malformation in Seahorses Attributed to the Oil Spill off the Brazilian Coast in 2019.

In 2019, there was an environmental catastrophe in Brazil, when more than 5000 tons of unknown origin crude oil invaded beaches and mangroves. Two years later, two monitoring areas were selected to study seahorses' offspring: Massangana River estuary (apparently healthy area) and Cocaia Island (affected area). Thirty-six reproductive events of Hippocampus reidi (Syngnathidae) couples from these two areas were monitored to analyze the offspring. At the apparently healthy area, no newborns with malformations were found. However, the offspring from Cocaia Island showed a mean of 19.73% (±5.23) malformations in newborns. It is argued that the toxic/teratogenic effects of polycyclic aromatic hydrocarbons have affected the population in two ways: directly through the induction of mutations in the germ cells of the species and through a drastic reduction of the population (bottleneck effect) whose density observed today recovered through consanguineous couplings, potentiating deleterious genotypes in the offspring. Environ Toxicol Chem 2024;00:1-9. © 2024 SETAC.

Local activation of CB1 receptors by synthetic and endogenous cannabinoids dampens burst firing mode of reticular thalamic nucleus neurons in rats under ketamine anesthesia.

The reticular thalamic nucleus (RTN) is a thin shell that covers the dorsal thalamus and controls the overall information flow from the thalamus to the cerebral cortex through GABAergic projections that contact thalamo-cortical neurons (TC). RTN neurons receive glutamatergic afferents fibers from neurons of the sixth layer of the cerebral cortex and from TC collaterals. The firing mode of RTN neurons facilitates the generation of sleep-wake cycles; a tonic mode or desynchronized mode occurs during wake and REM sleep and a burst-firing mode or synchronized mode is associated with deep sleep. Despite the presence of cannabinoid receptors CB1 (CB1Rs) and mRNA that encodes these receptors in RTN neurons, there are few works that have analyzed the participation of endocannabinoid-mediated transmission on the electrical activity of RTN. Here, we locally blocked or activated CB1Rs in ketamine anesthetized rats to analyze the spontaneous extracellular spiking activity of RTN neurons. Our results show the presence of a tonic endocannabinoid input, since local infusion of AM 251, an antagonist/inverse agonist, modifies RTN neurons electrical activity; furthermore, local activation of CB1Rs by anandamide or WIN 55212-2 produces heterogeneous effects in the basal spontaneous spiking activity, where the main effect is an increase in the spiking rate accompanied by a decrease in bursting activity in a dose-dependent manner; this effect is inhibited by AM 251. In addition, previous activation of GABA-A receptors suppresses the effects of CB1Rs on reticular neurons. Our results show that local activation of CB1Rs primarily diminishes the burst firing mode of RTn neurons.

Beyond its preferential niche: Brucella abortus RNA down-modulates the IFN-γ-induced MHC-I expression in epithelial and endothelial cells.

Brucella abortus (Ba) is a pathogen that survives inside macrophages. Despite being its preferential niche, Ba infects other cells, as shown by the multiple signs and symptoms humans present. This pathogen can evade our immune system. Ba displays a mechanism of down-modulating MHC-I on monocytes/macrophages in the presence of IFN-γ (when Th1 response is triggered) without altering the total expression of MHC-I. The retained MHC-I proteins are located within the Golgi Apparatus (GA). The RNA of Ba is one of the PAMPs that trigger this phenomenon. However, we acknowledged whether this event could be triggered in other cells relevant during Ba infection. Here, we demonstrate that Ba RNA reduced the surface expression of MHC-I induced by IFN-γ in the human bronchial epithelium (Calu-6), the human alveolar epithelium (A-549) and the endothelial microvasculature (HMEC) cell lines. In Calu-6 and HMEC cells, Ba RNA induces the retention of MHC-I in the GA. This phenomenon was not observed in A-549 cells. We then evaluated the effect of Ba RNA on the secretion of IL-8, IL-6 and MCP-1, key cytokines in Ba infection. Contrary to our expectations, HMEC, Calu-6 and A-549 cells treated with Ba RNA had higher IL-8 and IL-6 levels compared to untreated cells. In addition, we showed that Ba RNA down-modulates the MHC-I surface expression induced by IFN-γ on human monocytes/macrophages via the pathway of the Epidermal Growth Factor Receptor (EGFR). So, cells were stimulated with an EGFR ligand-blocking antibody (Cetuximab) and Ba RNA. Neutralization of the EGFR to some extent reversed the down-modulation of MHC-I mediated by Ba RNA in HMEC and A-549 cells. In conclusion, this is the first study exploring a central immune evasion strategy, such as the downregulation of MHC-I surface expression, beyond monocytes and could shed light on how it persists effectively within the host, enduring unseen and escaping CD8+ T cell surveillance.

Impaired Cardiac Sympathetic Activity Is Associated With Myocardial Remodeling and Established Biomarkers of Heart Failure.

BACKGROUND: 123Iodine-meta-iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. METHODS AND RESULTS: Prospectively enrolled patients with HF (New York Heart Association class II-III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart-to-mediastinum ratio from 123iodine-meta-iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT-proBNP [N-terminal pro-B-type natriuretic peptide], 248 [interquartile range, 79-574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT-proBNP, 743 [interquartile range, 250-2054] pg/dL) and 20 controls (LVEF, 65±5%; NT-proBNP, 40 [interquartile range, 19-50] pg/dL). Delayed (4 hours) 123iodine-meta-iodobenzylguanidine heart-to-mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P<0.001), and correlated negatively with diffuse fibrosis assessed by ECV (R=-0.34, P<0.01). ECV in segments without LGE was increased in HF with preserved ejection fraction (0.32±0.05%) and HF with reduced left ventricular ejection fraction (0.31±0.04%) versus controls (0.28±0.04, P<0.05) and was associated with the age- and sex-adjusted maximum oxygen consumption (peak oxygen consumption); (R=-0.41, P<0.01). Preliminary analysis indicates that cardiac sympathetic function might potentially act as a mediator in the association between ECV and NT-proBNP levels. CONCLUSIONS: Abnormally low cardiac sympathetic function in patients with HF with reduced and preserved LVEF is associated with extracellular volume expansion and decreased cardiopulmonary functional capacity.

Incarcerated Bochdalek Hernia in Adults.

In this case report, the diagnostic challenge and emergency management of a Bochdalek hernia in adults in Mexico are outlined. This case report can help the medical community to consider the clinical presentation in adults and the importance of early diagnosis and management. We present a 57-year-old female patient with a history of arterial hypertension who, following a bout of abdominal pain, was diagnosed with a Bochdalek hernia. Following emergency surgery, there was an increase in intra-abdominal pressure, which was continuously monitored due to the possibility of compartment syndrome, potentially necessitating a second emergency surgery.

Carbohydrate antigen 125 on epicardial fat and its association with local inflammation and fibrosis-related markers.

BACKGROUND: Carbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis. METHODS: Epicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively. RESULTS: The median age was 71 (63-74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels. CONCLUSION: Epicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis).

Acute Postnatal Inflammation Alters Adult Microglial Responses to LPS that Are Sex-, Region- and Timing of Postnatal Inflammation-Dependent.

BACKGROUND: Adverse events in early life can have impact lasting into adulthood. We investigated the long-term effects of systemic inflammation during postnatal development on adult microglial responses to LPS in two CNS regions (cortex, cervical spinal cord) in male and female rats. METHODS: Inflammation was induced in Sprague-Dawley rats by lipopolysaccharide (LPS, 1 mg/kg) administered intraperitoneally during postnatal development at P7, P12 or P18. As adults (12 weeks of age), the rats received a second LPS dose (1 mg/kg). Control rats received saline. Microglia were isolated 3 hours post-LPS from the cortex and cervical spinal cord. Gene expression was assessed via qRT-PCR for pro-inflammatory (IL-6, iNOS, Ptgs2, C/EBPb, CD14, CXCL10), anti-inflammatory (CD68, Arg-1), and homeostatic genes (P2Y12, Tmemm119). CSF-1 and CX3CL1 mRNA was analyzed in microglia-free homogenates. RESULTS: Basal gene expression in adult microglia was largely unaffected by early life LPS. Changes in adult microglial pro-inflammatory genes in response to LPS were either unchanged or attenuated in rats exposed to LPS during postnatal development. Ptgs2, C/EBPb, CXCL10 and Arg-1 were the genes most affected, with expression levels significantly downregulated vs control rats without postnatal LPS exposure. Cortical microglia were affected more by postnatal inflammation than spinal microglia, and males were more impacted than females. Overall, inflammatory challenge at P18 had the greatest effect on adult microglial gene expression, whereas challenge at P7 had less impact. Microglial homeostatic genes were unaffected by postnatal LPS. CONCLUSIONS: Long-lasting effects of postnatal inflammation on adult microglia depend on the timing of postnatal inflammation, CNS region and sex.

Development and validation of the Emotion Regulation Questionnaire - Positive/Negative (ERQ-PN): Does the target of emotion regulation matter?

The Emotion Regulation Questionnaire (ERQ) assesses emotion regulation strategies, particularly expressive suppression and cognitive reappraisal. However, the ERQ does not discern between regulating positive vs. negative emotions. Recent research suggests that suppression and reappraisal can impact mental health differently when targeting positive vs negative emotions. We developed and validated the Emotion Regulation Questionnaire - Positive/Negative (ERQ-PN), designed to measure positive and negative forms of suppression and reappraisal strategies. We recruited 963 participants (female = 478) through Prolific.com and administered the ERQ-PN. Participants had an average age of 45 years and were predominantly White (74%) and heterosexual (84%). Structural validity was assessed through confirmatory factor analyses. Model fit was estimated using the comparative fit index and the root-mean-square error of approximation. We also used the Bayesian information criterion to compare the fit of different models. Overall, participants used reappraisal more often to decrease negative emotions (vs. increasing positive) and leaned toward using suppression more for negative (vs. positive) emotions. These analyses revealed that the four-factor model (Model 2) delineating four latent variables (positive reappraisal, negative reappraisal, positive suppression, and negative suppression) had a good fit (RMSEA = 0.07, CFI = 0. 97, TLI = 0.96, χ 2 (98) = 531.28, p < 0.001). An incremental validity assessment revealed that positive and negative reappraisal correlated similarly with related mental health constructs. By contrast, suppression of negative vs. positive emotions was differentially associated to the validators tested. The ERQ-PN represents a valid measure of emotion regulation that accounts for both positive and negative emotions.

Eco(geno)toxicity of the new commercial insecticide Platinum Neo, a mixture of the neonicotinoid Thiamethoxam and the pyrethroid Lambda-Cyhalothrin.

New mixtures of pesticides are being placed on the market to increase the spectrum of phytosanitary action. Thus, the eco(geno)toxic effects of the new commercial mixture named Platinum Neo, as well as its constituents the neonicotinoid Thiamethoxam and the pyrethroid Lambda-Cyhalothrin, were investigated using the species Daphnia magna, Raphidocelis subcapitata, Danio rerio, and Allium cepa L. The lowest- and no-observed effect concentration (LOEC and NOEC) were measured in ecotoxicological tests. While Thiamethoxam was ecotoxic at ppm level, Lambda-Cyhalothrin and Platinum Neo formulation were ecotoxic at ppb level. The mitotic index (MI), chromosomal aberrations and micronucleus [MN] frequency were measured as indicators of phytogenotoxicity in A. cepa plants exposed for 12 hours to the different insecticides and their mixture under different dilutions. There were significant alterations in the MI and MN frequency in comparison with the A. cepa negative control group, with Thiamethoxam, Lambda-Cyhalothrin, and Platinum Neo treatments all significantly reducing MI and increasing MN frequency. Thus, MI reduction was found at 13.7 mg L-1 for Thiamethoxam, 0.8 µg L-1 for Lambda-Cyahalothrin, and 2.7:2 µg L-1 for Platinum Neo, while MN induction was not observed at 14 mg L-1 for Thiamethoxam, 0.8 µg L-1 for Lambda-Cyahalothrin, and 1.4:1 µg L-1 for Platinum Neo. The insecticide eco(geno)toxicity hierarchy was Platinun Neo > Lambda-Cyhalothrin > Thiamethoxam, and the organism sensitivity hierarchy was daphnids > fish > algae >A. cepa. Eco(geno)toxicity studies of new pesticide mixtures can be useful for management, risk assessment, and avoiding impacts of these products on living beings.

Protecting TiS3 Photoanodes for Water Splitting in Alkaline Media by TiO2 Coatings.

Titanium trisulfide (TiS3) nanoribbons, when coated with titanium dioxide (TiO2), can be used for water splitting in the KOH electrolyte. TiO2 shells can be prepared through thermal annealing to regulate the response of TiS3/TiO2 heterostructures by controlling the oxidation time and growth atmosphere. The thickness and structure of the TiO2 layers significantly influence the photoelectrocatalytic properties of the TiS3/TiO2 photoanodes, with amorphous layers showing better performance than crystalline ones. The oxide layers should be thin enough to transfer photogenerated charge through the electrode-electrolyte interface while protecting TiS3 from KOH corrosion. Finally, the performance of TiS3/TiO2 heterostructures has been improved by coating them with various electrocatalysts, NiSx being the most effective. This research presents new opportunities to create efficient semiconductor heterostructures to be used as photoanodes in corrosive alkaline aqueous solutions.

Blood Flow Restriction Enhances Recovery After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating neuromuscular and clinical outcomes of blood flow restriction (BFR) training after anterior cruciate ligament reconstruction (ACLR) compared to non-BFR rehabilitation protocols. METHODS: A systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines by querying PubMed, MEDLINE, Scopus, the Cochrane Database for Systematic Review, and the Cochrane Central Register for Controlled Trials databases from inception through December 2023 to identify Level I-II RCTs evaluating outcomes of BFR training after ACLR compared to non-BFR rehabilitation. A meta-analysis was performed using random-effects models with standardized mean difference (SMD) for pain, muscle strength, and muscle volume, while mean difference (MD) was calculated for patient-reported outcome measures. RESULTS: Eight RCTs, consisting of 245 patients, met inclusion criteria, with 115 patients undergoing non-BFR rehabilitation versus 130 patients undergoing BFR after ACLR. Mean patient age was 27.2 ± 6.7 years, with the majority of patients being male (63.3%, n=138/218). The length of the BFR rehabilitation protocol was most commonly between 8-12 weeks (range, 14 days - 16 weeks). The majority of studies set the limb/arterial occlusion pressure in the BFR group at 80%. When compared to non-BFR rehabilitation, BFR resulted in significant improvement in isokinetic muscle strength (SMD: 0.77, p=0.02, I2: 58%), IKDC score (MD: 10.97, p=<.00001, I2: 77%), and pain (SMD: 1.52, p=.04, I2: 87%), but not quadriceps muscle volume (SMD: 0.28, p=0.43, I2: 76%). CONCLUSION: The use of BFR following ACLR led to improvements in pain, IKDC score and isokinetic muscle strength, with variable outcomes based on quadriceps strength, volume and thickness when compared to non-BFR rehabilitation.

Phage-host co-evolution has led to distinct generalized transduction strategies.

Generalized transduction is pivotal in bacterial evolution but lacks comprehensive understanding regarding the facilitating features and variations among phages. We addressed this gap by sequencing and comparing the transducing particle content of three different Salmonella Typhimurium phages (i.e. Det7, ES18 and P22) that share a headful packaging mechanism that is typically initiated from a cognate pac site within the phage chromosome. This revealed substantial disparities in both the extent and content of transducing particles among these phages. While Det7 outperformed ES18 in terms of relative number of transducing particles, both phages contrasted with P22 in terms of content. In fact, we found evidence for the presence of conserved P22 pac-like sequences in the host chromosome that direct tremendously increased packaging and transduction frequencies of downstream regions by P22. More specifically, a ca. 561 kb host region between oppositely oriented pac-like sequences in the purF and minE loci was identified as highly packaged and transduced during both P22 prophage induction and lytic infection. Our findings underscore the evolution of phage transducing capacity towards attenuation, promiscuity or directionality, and suggest that pac-like sequences in the host chromosome could become selected as sites directing high frequency of transduction.

Non-specific pleuritis: long-term follow-up outcomes.

BACKGROUND: The definitive etiology of nonspecific pleuritis (NSP), the influence of the type of pleural biopsy on clinical results and the minimum duration of follow-up is controversial. RESEARCH DESIGN AND METHODS: A retrospective, observational study of patients ≥ 18 years with NSP confirmed by closed pleural biopsy (CPB), local anesthesia pleuroscopy (LAP), or video-assisted thoracic surgery (VATS). RESULTS: A total of 167 patients were included (mean follow-up, 14.4 months), of which 25 (15%) were diagnosed within one month; [15 (60%) malignant]. Of the remaining 142 pleural effusions (PEf), 69 (48.6%) were idiopathic; 49 (34.5%) not-malignant and 24 (16.9%) malignant (4 mesotheliomas and 20 metastasic). The diagnosis of NSP was established by CPB (7; median time to diagnosis, 9.4 months), LAT (5; 15.8 months), and VATS (8; 13.5 months) (p = 0.606). Sixty-eight patients (40.7%) died during follow-up (mean time, 12 months). CONCLUSIONS: In a substantial percentage of patients diagnosed with NSP, a definitive diagnosis will not be obtained, a relevant number of patients will develop a malignant PEf. The diagnostic procedure used for the diagnosis of NSP does not seem to influence delay in the diagnosis of malignant PEf. The data obtained suggest that follow-up should be maintained for at least 24 months.

Strategic control of the cattle tick Rhipicephlaus microplus applied to rotational and silvopastoral grazing systems in subtropical areas.

This work evaluated if strategic control based on no more than three or four annual treatments is useful to control Rhipicephalus microplus infestations on cattle when it is applied to intensive rotational grazing and silvopastoral systems with high stocking rates in subtropical areas. In the intensive rotational grazing system, three annual treatments with chemical acaricides were applied on cattle in two different schemes: between spring and early summer and from late winter and late spring. Strategic control based on three treatments with chemical acaricides from late winter to late spring plus an additional fourth treatment in summer was tested in the silvopastoral system. In the intensive rotational grazing systems, the control schemes allow to reach a significant reduction in the tick load on cattle considering a time interval from spring to autumn. However, the efficacy levels were not high enough in some specific moments, namely, the tick counts of summer and autumn (there were not significant differences between treated and control groups). The scheme evaluated in the silvopastoral grazing system yielded better results than those tested for the intensive rotational system, because significant differences in tick load between treated and control groups were observed in all post-treatment counts and when the analysis was performed for the whole study period. However, values of efficacy in the count-by-count comparison were disparate, ranging from 64.1 to 99.7. Although the efficacy values obtained in the silvopastoral system were better than those of the rotational grazing systems, the total tick load on treated cattle in autumn was not low enough (mean abundance values 25.14 and 38.14). Ticks were more evenly distributed among hosts in late summer and autumn than in spring or early summer, where few hosts carry most of the ticks. Some management strategies as intensive rotational systems or silvopastoral structures can lead to a more efficient forage use, but they imply greater tick challenge than in extensive grazing systems. In these situations, the schemes of strategic control bases on three or four annual treatments should be complemented with additional tactical treatments in late summer or autumn.

First Bioprospecting Study of Skin Host-Defense Peptides in Odontophrynus americanus.

The adaptation of amphibians to diverse environments is closely related to the characteristics of their skin. The complex glandular system of frog skin plays a pivotal role in enabling these animals to thrive in both aquatic and terrestrial habitats and consists of crucial functions such as respiration and water balance as well as serving as a defensive barrier due to the secretion of bioactive compounds. We herein report the first investigation on the skin secretion of Odontophrynus americanus, as a potential source of bioactive peptides and also as an indicator of its evolutionary adaptations to changing environments. Americanin-1 was isolated and identified as a neutral peptide exhibiting moderate antibacterial activity against E. coli. Its amphipathic sequence including 19 amino acids and showing a propensity for α-helix structure is discussed. Comparisons of the histomorphology of the skin of O. americanus with other previously documented species within the same genus revealed distinctive features in the Patagonian specimen, differing from conspecifics from other Argentine provinces. The presence of the Eberth-Katschenko layer, a prevalence of iridophores, and the existence of glycoconjugates in its serous glands suggest that the integument is adapted to retain skin moisture. This adaptation is consistent with the prevailing aridity of its native habitat.

Onychocolone A produced by the fungus Onychocola sp. targets cancer stem cells and stops pancreatic cancer progression by inhibiting MEK2-dependent cell signaling.

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds. Extracts derived from the fungus Onychocola sp. CF-107644 were assayed via high throughput screening followed by bioassay-guided fractionation and resulted in the identification and isolation of six benzophenone derivatives with antitumoral activity: onychocolones A-F (#1-6). The structures of the compounds were established by spectroscopic methods, including ESI-TOF MS, 1D and 2D NMR analyses and X-ray diffraction. Compounds #1-4 significantly inhibited the growth of the pancreas tumoral cell lines, with low-micromolar Median Effective Doses (ED50s). Compound #1 (onychocolone A) was prioritized for further profiling due to its pro-apoptotic effect, which was further validated on 3D spheroids and pancreatic CSCs. Protein expression assays showed that the effect was mechanistically linked to the inhibition of MEK onco-signaling pathway. The efficacy of onychocolone A was also demonstrated in vivo by the reduction of tumor growth in a pancreatic xenograft mouse model generated by CSCs. Altogether, the data support that onychocolone A is a promising new small molecule for hit-to-lead development of a new treatment for PC.

Exploring the potential of horse amendment for the remediation of HCHs-polluted soils.

This study assessed for the first time the bioremediation potential of an organic horse amendment in soils contaminated with solid wastes of the obsolete pesticide lindane (α-hexachlorocyclohexane (α-HCH) = 80 mg kg-1, ß-HCH = 40 mg kg-1, γ,δ,ε-HCH≈10 mg kg-1) searching for a self-sufficient bio-based economy. Four treatments were implemented: polluted (PS, ΣHCHs = 130 mg kg-1) and control (CS, ΣHCHs = 1.24 mg kg-1) soils and the respective amended soils (APS and ACS). A commercial amendment, coming from organic wastes, was used for soil biostimulation (5% dry weight), and the temporal evolution of the enzymatic activity (dehydrogenase, ß-glucosidase activity, phenoloxidase, arylamidase, phosphatase, and urease) and HCHs concentration of the soils was evaluated over 55 days under controlled humidity and temperature conditions. The horse amendment positively influenced the physicochemical properties of the soil by reducing pH (from 8.3 to 8) and increasing the organic matter (TOC from 0.5 to 3.3%) and nutrient content (P and NH4+ from 24.1 to 13.7 to 142.1 and 41.2 mg kg-1, respectively). Consequently, there was a notable enhancement in the soil biological activity, specifically in the enzymatic activity of dehydrogenase, phenol-oxidase, phosphatase, and urease and, therefore, in HCH degradation, which increased from <1 to 75% after the incubation period. According to the chlorine position on the cyclohexane ring, the following ranking has been found for HCHs degradation: ß-HCH (46%) < Îµ-HCH (57%) < α-HCH (91%) ≈ Î´-HCH (91%) < Î³-HCH (100%). Pentachlorocyclohexene (PCCH) and 1,2,4-trichlorobenzene (1,2,4-TCB) were identified as HCHs degradation metabolites and disappeared at the end of the incubation time. Although further research is required, these preliminary findings suggest that organic amendments represent a sustainable, harmless, and cost-effective biostimulation approach for remediating soils contaminated with recalcitrant HCHs, boosting the circular economy.

[Effectiveness of the CNIC polypill in secondary cardiovascular prevention in the subgroup of patients of the NEPTUNO study using atorvastatin doses of 20 mg]. / Efectividad de la polipíldora CNIC en prevención cardiovascular secundaria en el subgrupo de pacientes del estudio NEPTUNO con dosis de atorvastatina de 20 mg.

Objective: To analyse the incidence and risk of recurrent major adverse cardiovascular events (MACE), level of risk factor control, treatment persistence and cost of the CNIC polypill version containing acetylsalicylic acid (ASA) 100 mg, atorvastatin 20 mg (A20), and ramipril 2.5, 5.0 or 10 mg in secondary cardiovascular prevention patients. Method: Subanalysis of the observational, retrospective, multicentre, NEPTUNO study in patients treated for two years with the CNIC polypill A20, the same monocomponents as single drugs, equipotent drugs, and other therapies. Results: 922 patients were included in each group. The risk of recurrent MACE was lower among CNIC A20 polypill users than all others (21%, 23% and 26% increased risk among the monocomponents, equipotent or other therapy cohorts, respectively; p < 0.05). The magnitude of the mean change in low-density lipoprotein cholesterol and blood pressure, as well as the increase in the proportion of patients achieving target goals, was also greater among patients treated with the CNIC A20 polypill than in any of the other cohorts (all p < 0.001). Treatment persistence was significantly higher in patients treated with the CNIC A20 polypill (p < 0.001) and was a less costly strategy than any other therapeutic option. Conclusions: In patients in secondary cardiovascular prevention, the CNIC A20 polypill (ASA 100 mg, atorvastatin 20 mg, and ramipril 2.5, 5.0 or 10 mg) constitutes a valid therapeutic option with similar benefits and outcomes to the version of the polypill with atorvastatin 40 mg.

Objetivo: Analizar la incidencia y el riesgo de eventos adversos cardiovasculares mayores (MACE) recurrentes, el nivel de control de factores de riesgo, la persistencia al tratamiento y el coste de la versión de la polipíldora CNIC que contiene 100 mg de ácido acetilsalicílico (AAS), 20 mg de atorvastatina (A20) y 2.5/5.0 ó 10 mg de ramipril en pacientes en prevención cardiovascular secundaria. Método: Subanálisis del estudio observacional, retrospectivo y multicéntrico NEPTUNO en pacientes tratados durante 2 años con la polipíldora CNIC A20, los mismos monocomponentes por separado, medicamentos equipotentes uotras terapias. Resultados: Se incluyeron 922 pacientes en cada grupo. El riesgo de sufrir un MACE recurrente en el grupode polipíldora CNIC A20 fue menor que en todas las demás cohortes (21%, 23% y 26% de aumento del riesgo en las cohortesde monocomponentes, equipotentes u otras terapias, respectivamente; p < 0.05). La magnitud del cambio en el colesterol unidoa lipoproteínas de baja densidad y la presión arterial, así como el incremento en la proporción de pacientes que alcanzaron losobjetivos establecidos, fueron mayores en los pacientes tratados con la polipíldora CNIC A20 que en cualquiera de las otrascohortes (p < 0.001). La persistencia al tratamiento fue mayor en los pacientes tratados con la polipíldora CNIC A20 (p < 0.001)y esta estrategia resultó ser menos costosa que cualquier otra opción terapéutica. Conclusiones: En pacientes en prevencióncardiovascular secundaria, la polipíldora CNIC A20 (AAS 100 mg; atorvastatina 20 mg; ramipril 2.5/5.0 ó 10 mg) constituye unaopción terapéutica válida con beneficios y resultados similares a la versión de la polipíldora con 40 mg de atorvastatina.

MedYOLO: A Medical Image Object Detection Framework.

Artificial intelligence-enhanced identification of organs, lesions, and other structures in medical imaging is typically done using convolutional neural networks (CNNs) designed to make voxel-accurate segmentations of the region of interest. However, the labels required to train these CNNs are time-consuming to generate and require attention from subject matter experts to ensure quality. For tasks where voxel-level precision is not required, object detection models offer a viable alternative that can reduce annotation effort. Despite this potential application, there are few options for general-purpose object detection frameworks available for 3-D medical imaging. We report on MedYOLO, a 3-D object detection framework using the one-shot detection method of the YOLO family of models and designed for use with medical imaging. We tested this model on four different datasets: BRaTS, LIDC, an abdominal organ Computed tomography (CT) dataset, and an ECG-gated heart CT dataset. We found our models achieve high performance on a diverse range of structures even without hyperparameter tuning, reaching mean average precision (mAP) at intersection over union (IoU) 0.5 of 0.861 on BRaTS, 0.715 on the abdominal CT dataset, and 0.995 on the heart CT dataset. However, the models struggle with some structures, failing to converge on LIDC resulting in a mAP@0.5 of 0.0.