Antifouling activity and ecotoxicological profile of the cyanobacterial oxadiazine nocuolin A.

Pursuing effective and biocompatible natural compounds to supplant current biocidal antifouling (AF) technologies remains crucial and challenging. Among natural products hosts, cyanobacteria are recognized as producers of bioactive secondary metabolites that are underexplored in terms of anti-biofilm and AF potential. Nocuolin A, a natural oxadiazine previously isolated and known to be produced by different cyanobacterial strains, has demonstrated bioactive potential, particularly against tumor cell lines. Considering this potential and its exquisite chemical structure, here nocuolin A was investigated as a potential natural AF agent through an integrative approach including AF bioactivity testing across distinct levels of biological organization, mode of action assessment, ecotoxicity evaluation, and ecological risk predictions. Nocuolin A was found to inhibit the settlement of mussel (Mytilus galloprovincialis) plantigrades (EC50 = 3.905 µM) while showing no toxicity to this biofouling species (LC50 > 100 µM). Additionally, while exhibiting no inhibitory activity against the growth of five marine biofilm-forming bacterial strains, it significantly suppressed the growth of the marine biofilm-forming diatom Navicula sp. (EC50 = 1.561 µM), and had a lethal effect on this diatom species (>3.1 µM). The AF targets of nocuolin A on mussel plantigrades revealed no correlation with acetylcholinesterase and tyrosinase metabolic processes; however, proteins involved in oxidative stress, muscle regulation, and energy production were highlighted. The results also provide insights into the ecological risk of nocuolin A, including its ecotoxicity against Artemia salina nauplii (LC50 = 2.480 µM), Amphibalanus amphitrite nauplii (LC50 = 0.0162 µM), and Danio rerio embryos (LC50 = 0.0584 µM). When matching these results with simulated environmental values, nocuolin A was deemed a considerable threat to the ecosystems. While this research highlights the AF activity of nocuolin A, it also emphasizes the potential adverse environmental impact when applied in preventive coatings.

A Chemical Toolbox to Unveil Synthetic Nature-Inspired Antifouling (NIAF) Compounds.

The current scenario of antifouling (AF) strategies to prevent the natural process of marine biofouling is based in the use of antifouling paints containing different active ingredients, believed to be harmful to the marine environment. Compounds called booster biocides are being used with copper as an alternative to the traditionally used tributyltin (TBT); however, some of them were recently found to accumulate in coastal waters at levels that are deleterious for marine organisms. More ecological alternatives were pursued, some of them based on the marine organism mechanisms' production of specialized metabolites with AF activity. However, despite the investment in research on AF natural products and their synthetic analogues, many studies showed that natural AF alternatives do not perform as well as the traditional metal-based ones. In the search for AF agents with better performance and to understand which molecular motifs were responsible for the AF activity of natural compounds, synthetic analogues were produced and investigated for structure-AF activity relationship studies. This review is a comprehensive compilation of AF compounds synthesized in the last two decades with highlights on the data concerning their structure-activity relationship, providing a chemical toolbox for researchers to develop efficient nature-inspired AF agents.

Unintentional Infusion of Insulin Into the Epidural Space During Labor.

Inadvertent injection of drugs into the epidural space has a potential for serious morbidity and is probably underestimated and underreported. A 39-year-old female with no medical history presented for delivery. An epidural catheter was requested and correctly placed. Continuous epidural infusion was chosen for labor analgesia. Six hours after the parturient complained about inefficient analgesia, a syringe swap with insulin was identified. Despite the risk of possibly neurotoxic preservatives in the insulin formulation, no neurological sequelae were observed. This case highlights the issue of wrong-route drug administration and the urgent need to adopt route-specific connections.

Novel metabolite madeirone and neomarinone extracted from Streptomyces aculeoletus as marine antibiofilm and antifouling agents.

Introduction: Biofouling poses a significant economic threat to various marine industries, leading to financial losses that can reach billions of euros annually. This study highlights the urgent need for effective alternatives to traditional antifouling agents, particularly following the global ban on organotin compounds. Material and methods: Streptomyces aculeolatus PTM-346 was isolated from sediment samples on the shores of the Madeira Archipelago, Portugal. The crude extract was fractionated using silica flash chromatography and preparative HPLC, resulting in two isolated marinone compounds: madeirone (1), a novel marinone derivative discovered in this study, and neomarinone (2). The antifouling activities of these compounds were tested against five marine bacterial species and the larvae of the mussel Mytilus galloprovincialis. Additionally, in silico and in vivo environmental toxicity evaluations of madeirone (1) and neomarinone (2) were conducted. Results: Madeirone (1) demonstrated significant antibiofilm efficacy, inhibiting Phaeobacter inhibens by up to 66%, Marinobacter hydrocarbonoclasticus by up to 60%, and Cobetia marina by up to 40%. Neomarinone (2) also exhibited substantial antibiofilm activity, with inhibition rates of up to 41% against P. inhibens, 40% against Pseudo-oceanicola batsensis, 56% against M. hydrocarbonoclasticus, 46% against C. marina, and 40% against Micrococcus luteus. The growth inhibition activity at the same concentrations of these compounds remained below 20% for the respective bacteria, highlighting their effectiveness as potent antibiofilm agents without significantly affecting bacterial viability. Additionally, both compounds showed potent effects against the settlement of Mytilus galloprovincialis larvae, with EC50 values of 1.76 µg/mL and 0.12 µg/mL for compounds (1) and (2), respectively, without impairing the viability of the targeted macrofouling species. In silico toxicity predictions and in vivo toxicity assays both support their potential for further development as antifouling agents. Conclusion: The newly discovered metabolite madeirone (1) and neomarinone (2) effectively inhibit both micro- and macrofouling. This distinct capability sets them apart from existing commercial antifouling agents and positions them as promising candidates for biofouling prevention. Consequently, these compounds represent a viable and environmentally friendly alternative for incorporation into paints, primers, varnishes, and sealants, offering significant advantages over traditional copper-based compounds.

Treatment patterns and preferences of people living with HIV starting or switching antiretroviral therapy: Real-world evidence from Portugal.

BACKGROUND: There is a lack of up-to-date real-life evidence on antiretroviral therapy (ART) strategies among people living with HIV (PLWH) in Portugal. This study aimed to describe the treatment strategy used in PLWH either initiating or switching ART. METHODS: Non-interventional, cross-sectional, multicenter study carried out between December 2019 and October 2021 in Portugal. RESULTS: A total of 237 PLWH were included in this study, 171 of whom were ART-experienced and 66 were ART-naïve. The study showed that triple regimens were the most common ART strategy and integrase strand transfer inhibitors-based therapy was the most frequently used therapeutic class in both ART-naïve and ART-experienced PLWH. Nevertheless, about a third of PLWH who started a triple regimen transitioned to a dual regimen. Patient-reported outcomes revealed high HIV literacy and similar ART preferences in both groups. CONCLUSIONS: This real-world study showed that triple regimens were the most widely used ART strategy, even after the European AIDS Clinical Society guidelines introduced the recommendation of a dual regimen for naïve patients. The cohorts of this study presented a high level of HIV literacy at the time of inclusion. Our findings highlighted that taking pills only once a day is considered a very important feature for most patients.

Newborn's neural representation of instrumental and vocal music as revealed by fMRI: A dynamic effective brain connectivity study.

Music is ubiquitous, both in its instrumental and vocal forms. While speech perception at birth has been at the core of an extensive corpus of research, the origins of the ability to discriminate instrumental or vocal melodies is still not well investigated. In previous studies comparing vocal and musical perception, the vocal stimuli were mainly related to speaking, including language, and not to the non-language singing voice. In the present study, to better compare a melodic instrumental line with the voice, we used singing as a comparison stimulus, to reduce the dissimilarities between the two stimuli as much as possible, separating language perception from vocal musical perception. In the present study, 45 newborns were scanned, 10 full-term born infants and 35 preterm infants at term-equivalent age (mean gestational age at test = 40.17 weeks, SD = 0.44) using functional magnetic resonance imaging while listening to five melodies played by a musical instrument (flute) or sung by a female voice. To examine the dynamic task-based effective connectivity, we employed a psychophysiological interaction of co-activation patterns (PPI-CAPs) analysis, using the auditory cortices as seed region, to investigate moment-to-moment changes in task-driven modulation of cortical activity during an fMRI task. Our findings reveal condition-specific, dynamically occurring patterns of co-activation (PPI-CAPs). During the vocal condition, the auditory cortex co-activates with the sensorimotor and salience networks, while during the instrumental condition, it co-activates with the visual cortex and the superior frontal cortex. Our results show that the vocal stimulus elicits sensorimotor aspects of the auditory perception and is processed as a more salient stimulus while the instrumental condition activated higher-order cognitive and visuo-spatial networks. Common neural signatures for both auditory stimuli were found in the precuneus and posterior cingulate gyrus. Finally, this study adds knowledge on the dynamic brain connectivity underlying the newborns capability of early and specialized auditory processing, highlighting the relevance of dynamic approaches to study brain function in newborn populations.

Proof of Concept of Natural and Synthetic Antifouling Agents in Coatings.

Marine biofouling, caused by the deposition and accumulation of marine organisms on submerged surfaces, represents a huge concern for the maritime industries and also contributes to environmental pollution and health concerns. The most effective way to prevent this phenomenon is the use of biocide-based coatings which have proven to cause serious damage to marine ecosystems. Several research groups have focused on the search for new environmentally friendly antifoulants, including marine and terrestrial natural products and synthetic analogues. Some of these compounds have been incorporated into marine coatings and display interesting antifouling activities caused by the interference with the biofilm-forming species as well as by the inhibition of the settlement of macroorganisms. This review highlights the proof-of-concept studies of emerging natural or synthetic antifouling compounds in coatings, from lab-made to commercial ones, performed between 2019 and 2023 and their results in the field or in in vivo laboratorial tests.

Repurposing antiplasmodial leads for cancer: Exploring the antiproliferative effects of N-cinnamoyl-aminoacridines.

Drug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compounds were evaluated in vitro against three cancer cell lines (MKN-28, Huh-7, and HepG2), and human primary dermal fibroblasts. One of the series displayed highly selective antiproliferative activity in the micromolar range against the three cancer cell lines tested, without any toxicity to non-carcinogenic cells.

Chalcone derivatives as promising antifoulants: Molecular optimization, bioactivity evaluation and performance in coatings.

Marine biofouling remains a huge concern for maritime industries and for environmental health. Although the current biocide-based antifouling coatings can prevent marine biofouling, their use has been associated with toxicity for the marine environment, being urgent to find sustainable alternatives. Previously, our research group has identified a prenylated chalcone (1) with promising antifouling activity against the settlement of larvae of the macrofouling species Mytilus galloprovincialis (EC50 = 16.48 µM and LC50 > 200 µM) and lower ecotoxicity when compared to Econea®, a commercial antifouling agent in use. Herein, a series of chalcone 1 analogues were designed and synthesized in order to obtain optimized antifouling compounds with improved potency while maintaining low ecotoxicity. Compounds 8, 15, 24, and 27 showed promising antifouling activity against the settlement of M. galloprovincialis larvae, being dihydrochalcone 27 the most potent. The effect of compound 24 was associated with the inhibition of acetylcholinesterase activity. Among the synthesized compounds, compound 24 also showed potent complementary activity against Navicula sp. (EC50 = 4.86 µM), similarly to the lead chalcone 1 (EC50 = 6.75 µM). Regarding the structure-activity relationship, the overall results demonstrate that the substitution of the chalcone of the lead compound 1 by a dihydrochalcone scaffold resulted in an optimized potency against the settlement of mussel larvae. Marine polyurethane (PU)-based coatings containing the best performed compound concerning anti-settlement activity (dihydrochalcone 27) were prepared, and mussel larvae adherence was reduced compared to control PU coatings.

Unusual presentation of pancreatitis: Inguinoscrotal edema mimicking an incarcerated hernia - a case report.

INTRODUCTION: In rare instances, pancreatitis can manifest as inguinal edema without typical abdominal symptoms, posing diagnostic challenges. CASE PRESENTATION: We report a case of a man in his 40s, with alcohol addiction, who presented with left inguinal pain and swelling but no other abdominal complaints. Physical examination revealed inguinal tenderness and edema, with no hernia signs. Laboratory results showed leukocytosis and elevated C-reactive protein, inconsistent with the patient's symptoms. Abdominopelvic CT scan revealed peripancreatic fat densification and retroperitoneal fluid extending into the inguinal area. No hernia was evident. Extended analysis revealed elevated amylase and lipase levels, sustaining the diagnosis of pancreatitis. The patient responded well to supportive care and was discharged symptom-free. DISCUSSION: Acute pancreatitis emerging as an inguinoscrotal swelling, in the absence of any abdominal symptoms or signs, is extremely rare and can mimic more common causes of inguinoscrotal swellings, such as incarcerated hernias. This case highlights the ability of leaking pancreatic juice to track widely in the retroperitoneal tissues, particularly on the left side. A high level of suspicion, in combination with a CT scan, is essential for achieving an accurate diagnosis and determining the disease's extent. Failure to diagnose correctly could lead to unnecessary surgical procedures and inappropriate/delayed medical care. CONCLUSION: Inguinal edema as the sole presentation of acute pancreatitis is extremely rare. Therefore, it is essential to maintain a high index of suspicion, especially in patients with a history of alcohol consumption, in order to proceed with prompt treatment and avoid unnecessary surgery.

Pancreaticopleural fistula as the inaugural presentation of chronic pancreatitis: A case report.

INTRODUCTION: Pancreaticopleural fistula is a rare complication most associated with alcohol-induced chronic pancreatitis. This usually presents with chest symptoms instead of abdominal ones. Diagnosis requires a high index of suspicion in patients with pancreatitis and persistent pleural effusions. PRESENTATION OF CASE: We present a case of an 81-years-old man admitted in the emergency department with a one week complaints of productive cough, fever, dyspnea and left-side chest pain. The chest X-ray revealed a moderated-volume left-side pleural effusion. The pleural fluid analysis was consistent with an exsudative pleural effusion with high levels of amylase. The thoracoabdominal CT raised the suspicion of a pancreaticopleural fistula, confirmed by ERCP. A pancreatic main duct stenting was performed with good results. The patient was discharged asymptomatic after 18 days of hospitalization. DISCUSSION: Because of PPF insidious presentation it poses a great number of differential diagnosis, so pleural fluid analysis is of paramount importance with high levels of amylase confirming the diagnosis. MRCP and ERCP may establish the fistulous tract between the pancreatic duct and the pleural cavity, with the latter being also therapeutic. CONCLUSION: The rarity of this complication related to pancreatitis and the seldomly presence of abdominal pain in contrast with chest symptoms poses a diagnostic challenge.

Dexmedetomidine in Palliative Care: A Versatile New Weapon Against Delirium and Pain-Systematic Review.

Introduction: At the end of life, the prevalence of delirium and pain is high. Current therapy is not satisfactory. Dexmedetomidine could be useful in the control of delirium and pain but is not approved outside of intensive care setting. Our objectives are to evaluate existing evidence in the literature that assessed the efficacy of dexmedetomidine in pain and delirium control and its safety in palliative care patients outside intensive care units. This systematic review was prospectively registered with PROSPERO and included a risk of bias assessment. Methods: PubMed and SCOPUS were examined for literature published until 2023. Experimental, cohort, cross-sectional, case-control studies, and case series/reports were included if they evaluate the use of dexmedetomidine in delirium and/or pain management in hospitalized palliative care adult patients. Studies were excluded if they were carried out in intensive care units. Results: Of the initial 529 records, 14 were included. Although only two studies were randomized trials, most were small and only one had low risk of bias. In most case reports and in the two retrospective cohort studies, dexmedetomidine appears to be a better option for these symptoms, although differences were not significant in the randomized trials. Discussion: Dexmedetomidine seems to be a promising option for refractory pain and delirium and may contribute to a reduction in opioid administration to control pain. This is the first systematic review of dexmedetomidine in palliative care. Quality evidence is limited, but clinical properties of dexmedetomidine justify the conduction of controlled trials in palliative care.

Removal of chromium(III) from contaminated waters using cobalt ferrite: how safe is remediated water to aquatic wildlife?

The release of hazardous elements by industrial effluents to aquatic ecosystems is a potential threat to the environment. Chromium (Cr) is one of the elements whose levels in several freshwater ecosystems should be reduced to promote water reuse. In recent years, magnetic materials have gained increasing interest as sorbents because of their easy removal from treated water through magnetic separation. In this study, colloidal cobalt ferrite (CoFe2O4) particles were investigated as magnetic sorbents for chromium-aqueous chemical species. The oxidative stress responses of Mytilus galloprovincialis mussels exposed to 200 µg/L of Cr, resembling remediated water, were evaluated. More than 95% of Cr was removed from contaminated solutions by CoFe2O4 aqueous suspensions at pH 6 and pH 10. The kinetics of sorption experiments were examined using pseudo-1st order, pseudo-2nd order and Elovich models to evaluate which mathematical model has a better adjustment to the experimental data. The present study revealed that the levels of Cr that remained in remediated water induced limited biochemical changes in mussels, being considered safe for aquatic systems. Overall, the use of cobalt ferrite-based sorbents may constitute a promising approach to remediate contaminated water.

Application of three-dimensional imaging software to map carcinomatosis in recurrent ovarian cancer.

The treatment of recurrent ovarian cancer has been based on systemic therapy. The role of secondary cytoreductive surgery has been addressed recently in several trials. Imaging plays a key role in helping the surgical team to decide which patients will have resectable disease and benefit from surgery. The role of staging laparoscopy and several imaging and clinical scores has been extensively debated in the field. In other surgical fields there have been reports of using 3D imaging software and 3D printed models to help surgeons better plan the surgical approach. To the best of our knowledge, we report the first case of a patient with recurrent ovarian cancer undergoing 3D modeling before secondary cytoreductive surgery. The 3D modeling was of most value to evaluate the extension of the disease in our patient who underwent a successful secondary cytoreductive surgery and is currently free of the disease.

Enhanced removal of rare earth elements from aqueous media: exploring the potential of AM-3 and AM-4 titanosilicates.

This study investigates the impact of three key variables on the performance of nanoporous AM-3 and layered AM-4 titanosilicates in removing nine REEs (Y, La, Ce, Pr, Nd, Eu, Gd, Tb, and Dy) from natural mineral water and identifies optimal operational conditions using Response Surface Methodology (RSM). The experimental conditions were determined by a Box-Behnken Design of 3 factors-3 levels (pH 4, 6, and 8; sorbent dose 20, 100, and 180 mg/L; and element concentration 1, 3, and 5 µmol/L). Three-dimensional response surfaces were used to assess the linear, quadratic, and interaction influences of each factor on the REEs' removal percentage. The pH was the most significant factor in the removal process using AM-3, while the sorbent dose was more important for AM-4. The results highlighted the sorbents' strong capacity for REE removal. The optimal operating conditions obtained by RSM were applied to aqueous solutions with salinity 10 (common in coastal and transitional systems) and 30 (average seawater salinity). The results showed that AM-3 has a strong potential for removing REEs in solutions with salinity 10 and 30, while AM-4 was less efficient due to competition between REEs and other ions present in the solution.

The Role of Natural and Synthetic Flavonoids in the Prevention of Marine Biofouling.

Marine biofouling is a major concern for the maritime industry, environment, and human health. Biocides which are currently used in marine coatings to prevent this phenomenon are toxic to the marine environment, and therefore a search for antifoulants with environmentally safe properties is needed. A large number of scientific papers have been published showing natural and synthetic compounds with potential to prevent the attachment of macro- and microfouling marine organisms on submerged surfaces. Flavonoids are a class of compounds which are highly present in nature, including in marine organisms, and have been found in a wide range of biological activities. Some natural and synthetic flavonoids have been evaluated over the last few years for their potential to prevent the settlement and/or the growth of marine organisms on submerged structures, thereby preventing marine biofouling. This review compiles, for the first-time, natural flavonoids as well as their synthetic analogues with attributed antifouling activity against macrofouling and microfouling marine organisms.

Is combined MPFL reconstruction and tubercule tibial osteotomy superior to isolated reconstruction? A systematic review and meta-analysis.

Purpose: There is no consensus for management of patellar instability, even in the case of malalignment. The purpose of the review is to evaluate outcomes in the literature of MPFL reconstruction with and without tibial tubercle osteotomy. Methods: Two databases PubMed and Scopus were searched for studies comparing MPFL reconstruction with and without concomitant tibial tuberosity osteotomy. PRISMA guidelines were followed. Data on functional outcomes via Kujala score, redislocation rates and return to sport rates were reported. Results: 9 studies included data from 806 knees: 463 submitted to isolated MPFL reconstruction, and 343 submitted to the combined surgery. Patients submitted to the combined procedure had all TT-TG values superior to 18, while the ones with isolated reconstruction had more heterogeneous values, varying between 13 and 20 mm. 77.78% of the studies reported on postoperative Kujala scores, with a mean value of 83.53 in patients who underwent MPFL reconstruction alone and 83.72 in those who underwent the combined procedure. The mean difference between the two groups was -0.83, with the improvement of the score statistically significant in 22.22% of the studies, regardless of the surgery. Concerning redislocation rate, odds ratio comparing both procedures was 0.84 (p = 0.67). Conclusion: The principal finding is that the MPFL reconstruction with or without TTO resulted in similar functional outcomes, assessed by the Kujala score, and low complications concerning recurrent patellar dislocation. More robust literature is needed in the setting of a high TT-TG distance. Level of evidence: IV.

Solar-pumped dual-rod Ce:Nd:YAG laser with 58 W continuous-wave output power and 5.1° tracking error compensation width.

The pursuit of high-power solar laser systems with high efficiency and capacity for large tracking error compensation is determinant for the applicability of this renewable technology. A side-pumped dual-rod Ce:Nd:YAG solar laser was developed and tested at the focus of a 2 m diameter parabolic concentrator. Maximum continuous-wave total solar laser power of 58 W was measured. To the best of our knowledge, this is the highest laser power from a Ce:NdYAG solar laser. Moreover, wide tracking error compensation width of 5.1° in the azimuthal direction was reached, being 4.25 times higher than the previous measurement without solar tracking assistance.

Intersectionality, vulnerability and foot health inequity.

Foot health and wellbeing in the UK are often overlooked in healthcare. Foot health outcomes are strongly interlinked to the social determinants of health, in that the way these determinants intersect can impact an individual's vulnerability to foot pain and disorders. In this commentary we explore some social determinants that hinder individuals from improving their foot health behaviour and ultimately reducing foot pain and foot disorder vulnerability. We focus on socioeconomic status, gender, disability, age, culture and ethnicity, and footwear quality; we also highlight the potential impact of the Covid-19 pandemic and the cost-of-living crisis on foot health inequities; rises in inflation have resulted in footcare becoming less affordable among vulnerable groups, like those with intellectual disabilities and chronic illness, older people, those living in rural and inner-city communities, and the ethnically and linguistically diverse population living in the UK. There is an urgent need to raise awareness of the social determinants of foot health, their intersectionality, and their impact on foot pain and disorder vulnerability. Despite the Black Report and both Marmot Reviews, little progress has been made in raising this awareness. It is recommended to widen the range of foot health interventions, by including it in GP consultations, developing cultural sensitivity within foot health services, creating more comprehensive educational foot health programmes, and developing a more sustainable footwear industry.