A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver.

Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine's half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.

Electroactive poly(vinylidene fluoride-trifluoroethylene)/graphene composites for cardiac tissue engineering applications.

Electroactive materials are increasingly being used in strategies to regenerate cardiac tissue. These materials, particularly those with electrical conductivity, are used to actively recreate the electromechanical nature of the cardiac tissue. In the present work, we describe a novel combination of poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)), a highly electroactive polymer, with graphene (G), exhibiting high electrical conductivity. G/P(VDF-TrFE) films have been characterized in terms of topographical, physico-chemical, mechanical, electrical, and thermal properties, and studied the response of cardiomyocytes adhering to them. The results indicate that the crystallinity and the wettability of the composites remain almost unaffected after G incorporation. In turn, surface roughness, Young modulus, and electric properties are higher in G/P(VDF-TrFE). Finally, the composites are highly biocompatible and able to support cardiomyocyte adhesion and proliferation, particularly surface treated ones, demonstrating the suitability of these materials for cardiac tissue engineering applications.

Spatial accumulation of flood-driven riverside litter in two Northern Atlantic Rivers.

The escalation of litter accumulation in aquatic environments is recognized as an emerging global concern. Although rivers represent the main conduits for land-based waste into the oceans, the spatial dynamics of litter accumulation in these systems remain poorly investigated, especially after hydro-climatic extreme events. Floods have been identified as major drivers of litter mobilization, including macroplastics, within rivers. However, predicting flood-induced litter accumulation along riverbanks is complex due to the cumulative interplay of multiple environmental (geomorphological and riparian) and anthropogenic factors. Using empirical data collected from 14 stream reaches in two Northern Atlantic rivers in Portugal, our study evaluates which factors, among geomorphological, riparian, and anthropogenic descriptors, best drive riverside litter accumulation after floods. Taking into account the longitudinal gradient and the spatial heterogeneity of the studied reaches, our study enhances how the accumulation and characteristics (type, size) of riverside litter vary across a rural-urban continuum. Our model reveals that the combination of the human population density and the stream slope at river reach showed the highest explanatory power for the accumulation of riverside litter. Our findings indicate that litter tends to be retained close to the source, even under flood conditions. We also found that the structure of riparian vegetation showed low explanatory power for litter accumulation. However, riparian trapping could be influenced by litter input (density and type) which varies with anthropogenic activities. This work highlights the importance of gathering field data to identify critical areas of riverside litter accumulation within river basins. Our findings can further support environmental managers in designing and implementing effective cleanup campaigns and implementing plastic recovery strategies at specific areas. Nevertheless, it is crucial to enhance coordinated efforts across the entire value chain to reduce plastic pollution, promote innovative approaches for plastic litter valorization, and establish effective prevention pathways.

Beyond activity patterns: The complex process of activity management among individuals with chronic musculoskeletal pain after an orthopaedic trauma.

CONTEXT: Individuals must change the way they perform activities in response to chronic pain. In the literature, three activity patterns are commonly described: avoidance, pacing, and persistence. Many studies have explored these activity patterns. However, little research has delved into the factors that lead people to adopt a particular activity behaviour. This study aimed to explore the relationship that people with chronic musculoskeletal pain have with activity and highlight the factors underlying their practices. METHODS: The qualitative study was conducted by researchers in the social sciences, physiotherapy, psychology, and rehabilitation medicine. Observations of vocational workshops and semi-structured interviews were conducted with 33 persons undergoing rehabilitation for chronic musculoskeletal pain after an accident. RESULTS: Patients' declarations and actions show that any one patient will alternate between activity patterns: the same person may adopt a strategy of avoidance, pacing or persistence depending on the context, the importance of the activity, personal objectives, and representations of self, pain, and activity. The decision to engage in a particular behaviour is based on a process of self-negotiation weighted by the circumstances, the nature of the activity, the importance attached to it, and the individual's perceived ability. CONCLUSION: Our study emphasized the complexity of physical, social, and contextual factors that intervene in the relationship toward activity. Rather than favouring pacing, the therapist's role in rehabilitation might be to reinforce the reflexive process and the patient's adaptability in approaching the activity, to foster the capacity to find flexible solutions. SIGNIFICANCE: Patients choose an activity pattern (avoidance, pacing, persistence) according to the challenges they face in their daily lives. Context, representations of self and activity, as well as goals sought influence these choices. Some patients report having learned to adapt their activity management strategies. Therefore, therapeutic approaches in the rehabilitation context could focus on these adaptive capacities to offer patients optimal pain and activity management and develop their ability to use different strategies according to the circumstance.

Enantioselectivity in ecotoxicity of pharmaceuticals, illicit drugs, and industrial persistent pollutants in aquatic and terrestrial environments: A review.

At present, there is a serious concern about the alarming number of recalcitrant contaminants that can negatively affect biodiversity threatening the ecological status of marine, estuarine, freshwater, and terrestrial ecosystems (e.g., agricultural soils and forests). Contaminants of emerging concern (CEC) such as pharmaceuticals (PHAR), illicit drugs (ID), industrial persistent pollutants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and chiral ionic solvents are globally spread and potentially toxic to non-target organisms. More than half of these contaminants are chiral and have been measured at different enantiomeric proportions in diverse ecosystems. Enantiomers can exhibit different toxicodynamics and toxicokinetics, and thus, can cause different toxic effects. Therefore, the enantiomeric distribution in occurrence cannot be neglected as the toxicity and other adverse biological effects are expected to be enantioselective. Hence, this review aims to reinforce the recognition of the stereochemistry in environmental risk assessment (ERA) of chiral CEC and gather up-to-date information about the current knowledge regarding the enantioselectivity in ecotoxicity of PHAR, ID, persistent pollutants (PCBs and PBDEs) and chiral ionic solvents present in freshwater and agricultural soil ecosystems. We performed an online literature search to obtain state-of-the-art research about enantioselective studies available for assessing the impact of these classes of CEC. Ecotoxicity assays have been carried out using organisms belonging to different trophic levels such as microorganisms, plants, invertebrates, and vertebrates, and considering ecologically relevant aquatic and terrestrial species or models organisms recommended by regulatory entities. A battery of ecotoxicity assays was also reported encompassing standard acute toxicity to sub-chronic and chronic assays and different endpoints as biomarkers of toxicity (e.g., biochemical, morphological alterations, reproduction, behavior, etc.). Nevertheless, we call attention to the lack of knowledge about the potential enantioselective toxicity of many PHAR, ID, and several classes of industrial compounds. Additionally, several questions regarding key species, selection of most appropriate toxicological assays and ERA of chiral CEC are addressed and critically discussed.

Respiratory oscillometry and functional analyses in patients with idiopathic scoliosis.

Scoliosis is a condition that affects the spine and causes chest rotation and trunk distortion. Individuals with severe deformities may experience dyspnea on exertion and develop respiratory failure. Respiratory oscillometry is a simple and non-invasive method that provides detailed information on lung mechanics. This work aims to investigate the potential of oscillometry in the evaluation of respiratory mechanics in patients with scoliosis and its association with physical performance. We analyzed 32 volunteers in the control group and 32 in the scoliosis group. The volunteers underwent traditional pulmonary function tests, oscillometry, and the 6-minute walk test (6MWT). Oscillometric analysis showed increased values of resistance at 4 Hz (R4, P<0.01), 12 Hz (R12, P<0.0001), and 20 Hz (R20, P<0.01). Similar analysis showed reductions in dynamic compliance (Cdyn, P<0.001) and ventilation homogeneity, as evaluated by resonance frequency (fr, P<0.001) and reactance area (Ax, P<0.001). Respiratory work, described by the impedance modulus, also showed increased values (Z4, P<0.01). Functional capacity was reduced in the group with scoliosis (P<0.001). A significant direct correlation was found between Cobb angle and R12, AX, and Z4 (P=0.0237, P=0.0338, and P=0.0147, respectively), and an inverse correlation was found between Cdyn and Cobb angle (P=0.0190). These results provided new information on respiratory mechanics in scoliosis and are consistent with the involved pathophysiology, suggesting that oscillometry may improve lung function tests for patients with scoliosis.

Glomerulocystic kidney in two red piranhas Pygocentrus nattereri.

Glomerulocystic kidney (GCK) is defined by a dilatation of the Bowman's space (greater than 2 times the normal size) of more than 5% of all glomeruli. Although GCK has been occasionally documented in dogs, cats, and humans with renal failure, in fish, reports of spontaneous GCK are rare. For the present study, 2 captive adult red piranhas Pygocentrus nattereri from a closed population were submitted for post-mortem examination. Clinical history included lethargy, inappetence, dyspnea, and altered buoyancy. Macroscopically, the fish displayed coelomic distension and ascites. The kidneys were markedly enlarged and dark yellow. Histologically, Bowman's space was noticeably dilated, occasionally with atrophic glomerular tufts. Degeneration and necrosis of the tubular epithelium, infiltration, and nephrocalcinosis were also present. To the authors' knowledge, this present study is the first report of spontaneously occurring GCK in red piranhas and freshwater fish in general. Despite being rare, GCK is a condition with the potential to impair the health of fish and mammals, and further studies are needed to shed new light on this condition.

Allergic emergencies in the prehospital setting: a 5 year retrospective study.

Summary: Background. Patients with severe allergic conditions often request support from the prehospital emergency services given the rapid, unexpected and potentially life-threatening nature of the reactions, such as anaphylaxis. Studies regarding prehospital incidents for allergic conditions are scarce. This study aimed to characterize prehospitalar medical requesting assistance due to suspected hypersensitivity reactions (HSR). Methods. Retrospective study of allergic-related requesting assistances between 2017-2022 of a Portuguese emergency dispatch centre - Emergency and Resuscitation Medical Vehicle (VMER), in Coimbra University Hospital. Demographic and clinical variables were analysed, including clinical manifestations, anaphylaxis severity grading, therapeutic interventions, and post-incident allergic work-up. Regarding anaphylactic events, three diagnosis timings were compared: on-site, hospital emergency department and Investigator-diagnosis based on data reviewed. Results. Out of 12689 VMER requesting assistances, 210 (1.7%) were classified as suspected HSR reactions. After on-site medical evaluation, 127 (60.5%) cases maintained the HSR classification (median age 53 years; 56% males) and the main diagnoses included HSR to Hymenoptera venom (29.9%), food allergy (29.1%), and pharmaceutical drugs (25.5%). Anaphylaxis was assumed on-site in 44 (34.7%) cases, in the hospital emergency department in 53 cases (41.7%) and by investigators in 76 (59.8%) cases. Regarding management, epinephrine was administered on-site in 50 cases (39.4%). Conclusions. The main reason for prehospital requesting assistance was HSR to Hymenoptera venom. A high proportion of incidents met the criteria for anaphylaxis and despite the inherent difficulties of the prehospital setting, many of the on-site diagnoses agreed with the criteria. Regarding management, epinephrine was underused in this setting. Referral to specialized consultation is crucial for the management of prehospital incidents.

Earlier biomarkers in fish evidencing stress responses to metal and organic pollution along the Doce River Basin.

The Doce River Basin (DRB) represents a well-described watershed in terms of contamination by metals, especially after a major environmental disaster of a mining tailing dam failure. Despite the massive mortality of the ichthyofauna, very few studies addressed the risks to the health of wild fish exposed to complex mixtures of pollutants from multiple sources. The present study proposed to investigate earlier responses of fish for assessing the impacts of multiple sources of pollution, considering: different niches of fish and target organs; and the influence of seasonality, associated with their probable sources of pollution. To achieve that, fish were collected along the DRB, and biomarkers responses were assessed in target organs and correlated with the levels of inorganic and organic contaminants. As one of the most prominent responses, fishes from the Upper DRB showed the highest expression of the metallothionein and oxidative stress parameters which were related to the higher levels of metals in this region due to the proximity of mining activities. On the other hand, higher levels of DNA damage and increased AChE activity from fish sampled in the Mid and Lower DRB were more associated with organic contaminants, from other sources of pollution than mining residues. The integrated biomarker responses also revealed seasonal variations, with higher values in fishes from the dry season, and pelagic fish showing greater variation within the seasons. The multivariate analysis integrating suitable biomarkers with chemical data represented an adequate strategy for assessing the ecological risks in the DRB, allowing the identification of distinct spatio-temporal impacts from multiple sources of contaminants. The continued exposure of the ichthyofauna representing future risks reinforces the need for ecological restoration and the protection of the fauna from the Doce River.

Accuracy and safety of 3D printed surgical guides combined with monitored guidewires for placement of cervicothoracic pedicle screws: Technical note.

Subaxial cervical pedicle screws provide rigid fixation, but their placement poses an important neurovascular injury risk. 3D printed guides have successfully been used to place pedicle screws, but experience in the subaxial cervical spine is limited. We present a case of cervicothoracic dissociation after a pathological fracture due to tumour involvement of the upper thoracic spine, causing paraparesis and intense pain. The cervicothoracic junction is of difficult visualization on fluoroscopy and the patients' severe instability made navigation unreliable. 3D printed individualized guidewire guides were used to help place canulated pedicle screws from C4 to T6. We successfully report the use of impedance guidewire monitoring to prevent pedicle violation and improve procedure safety.

Improving the Performance of Paper-Based Dipole Antennas by Electromagnetic Flux Concentration.

One of the essential issues in modern advanced materials science is to design and manufacture flexible devices, in particular in the framework of the Internet of Things (IoT), to improve integration into applications. An antenna is an essential component of wireless communication modules and, in addition to flexibility, compact dimensions, printability, low cost, and environmentally friendlier production strategies, also represent relevant functional challenges. Concerning the antenna's performance, the optimization of the reflection coefficient and maximum range remain the key goals. In this context, this work reports on screen-printed paper@Ag-based antennas and optimizes their functional properties, with improvements in the reflection coefficient (S11) from -8 to -56 dB and maximum transmission range from 208 to 256 m, with the introduction of a PVA-Fe3O4@Ag magnetoactive layer into the antenna's structure. The incorporated magnetic nanostructures allow the optimization of the functional features of antennas with possible applications ranging from broadband arrays to portable wireless devices. In parallel, the use of printing technologies and sustainable materials represents a step toward more sustainable electronics.

Magnesium incorporation in fibrinogen scaffolds promotes macrophage polarization towards M2 phenotype.

The host inflammatory response to biomaterials conditions their capacity to promote tissue repair, and macrophage polarization shift from M1 to M2 is determinant in this process. Previous work showed that extracts of a combination between fibrinogen and metallic magnesium materials acted synergistically to reduce macrophage inflammatory phenotype. The hypothesis underlying the current work was that the ability of magnesium-modified fibrinogen scaffolds to modulate macrophage phenotype depends on the concentration of magnesium. Thus, Fibrinogen (Fg) scaffolds incorporating precise concentrations of magnesium sulfate (Mg: 0, 10, 25, 50 mM) were developed and characterized. Mg incorporation in Fg scaffolds increased surface charge, while porosity decreased with increasing Mg concentrations, but only Fg scaffolds with 10 mM of Mg (FgMg10) had significantly improved mechanical properties. Human macrophages cultured on FgMg10 scaffolds, showed increased M2 and decreased M1 polarization, when compared to those cultured on scaffolds with 0, 25 and 50 mM of Mg. Macrophage polarization results were independent of the anion used (chloride or sulfate). Macrophage modulation by FgMg10 scaffolds involved reduced NF-κB p65 nuclear translocation, and impacted production of pro-inflammatory mediators (e.g. IFNγ, IL-12, TNF-⍺, IP-10). Importantly, FgMg10 scaffolds implanted in vivo increased the expression of M2 marker CD163, in macrophages from inflammatory exudates, compared to Sham and Fg-implanted animals, increasing the M2:M1 ratio. A cytokine/chemokine array showed that, while both Fg and FgMg10 scaffolds decreased inflammatory mediators, only FgMg10 decreased IL-1ß, IP-10, MIP-2, MDC and MIP-3⍺, compared to Sham-operated animals. This study demonstrated that incorporation of 10mM of Mg modulated inflammation, promoting M2 macrophage polarization in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Developing biomaterials that can modulate inflammation and promote macrophage phenotype switch from M1 to M2 is crucial to promote a regenerative microenvironment. Our previous work showed that extracts of a combination between fibrinogen (Fg) and metallic magnesium (Mg) materials synergistically reduced macrophage pro-inflammatory phenotype. Herein, we tested the hypothesis that macrophage modulation was dependent on Mg concentration. A new family of Fg porous scaffolds incorporating different amounts of Mg (0, 10, 25 and 50 mM) was produced and characterized. We observed that only the combination of Fg scaffolds with 10 mM of Mg (FgMg10) significantly changed the scaffolds mechanical properties and directed macrophages towards a M2 phenotype, reducing the production of inflammatory mediators, both in vitro and in vivo.

Respiratory oscillometry and functional analyses in patients with idiopathic scoliosis

Scoliosis is a condition that affects the spine and causes chest rotation and trunk distortion. Individuals with severe deformities may experience dyspnea on exertion and develop respiratory failure. Respiratory oscillometry is a simple and non-invasive method that provides detailed information on lung mechanics. This work aims to investigate the potential of oscillometry in the evaluation of respiratory mechanics in patients with scoliosis and its association with physical performance. We analyzed 32 volunteers in the control group and 32 in the scoliosis group. The volunteers underwent traditional pulmonary function tests, oscillometry, and the 6-minute walk test (6MWT). Oscillometric analysis showed increased values of resistance at 4 Hz (R4, P<0.01), 12 Hz (R12, P<0.0001), and 20 Hz (R20, P<0.01). Similar analysis showed reductions in dynamic compliance (Cdyn, P<0.001) and ventilation homogeneity, as evaluated by resonance frequency (fr, P<0.001) and reactance area (Ax, P<0.001). Respiratory work, described by the impedance modulus, also showed increased values (Z4, P<0.01). Functional capacity was reduced in the group with scoliosis (P<0.001). A significant direct correlation was found between Cobb angle and R12, AX, and Z4 (P=0.0237, P=0.0338, and P=0.0147, respectively), and an inverse correlation was found between Cdyn and Cobb angle (P=0.0190). These results provided new information on respiratory mechanics in scoliosis and are consistent with the involved pathophysiology, suggesting that oscillometry may improve lung function tests for patients with scoliosis.

Greener Solvent-Based Processing of Magnetoelectric Nanocomposites.

Polymer-based magnetoelectric (ME) nanocomposites are an enabling material technology for a wide range of applications in the area of digitalization strategies. Due to its highest piezoelectric response among polymers, poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) is the piezoelectric matrix most used in polymer-based ME materials with over 80% of the total reports, with the resulting composites typically processed from solutions with N,N-dimethylformamide (DMF), a toxic solvent. Nevertheless, environmentally friendlier approaches and sustainable technologies are increasingly being required. This work demonstrates that P(VDF-TrFE)/Co2Fe2O4 nanocomposites can be successfully prepared from solution using three different environmentally friendlier solvents: dimethyl sulfoxide (DMSO), N,N'-dimethylpropyleneurea (DMPU), and triethyl phosphate (TEP) with different dipole moments. It is shown that the prepared composite films, with a maximum ME voltage coefficient of 35 mV cm-1 Oe-1 and a maximum sensitivity of 2.2 mV T-1, are suitable for applications, highlighting the path for a new generation of more sustainable ME sensors.

Surface charge and dynamic mechanoelectrical stimuli improves adhesion, proliferation and differentiation of neuron-like cells.

Neuronal diseases and trauma are among the current major health-care problems. Patients frequently develop an irreversible state of neuronal disfunction that lacks treatment, strongly reducing life quality and expectancy. Novel strategies are thus necessary and tissue engineering research is struggling to provide alternatives to current treatments, making use of biomaterials capable to provide cell supports and active stimuli to develop permissive environments for neural regeneration. As neuronal cells are naturally found in electrical microenvironments, the electrically active materials can pave the way for new and effective neuroregenerative therapies. In this work the influence of piezoelectric poly(vinylidene fluoride) with different surface charges and dynamic mechanoelectrical stimuli on neuron-like cells adhesion, proliferation and differentiation was addressed. It is successfully demonstrated that both surface charge and electrically active dynamic microenvironments can be suitable to improve neuron-like cells adhesion, proliferation, and differentiation. These findings provide new knowledge to develop effective approaches for preclinical applications.

Necrotic-like BV-2 microglial cell death due to methylmercury exposure.

Methylmercury (MeHg) is a dangerous environmental contaminant with strong bioaccumulation in the food chain and neurotoxic properties. In the nervous system, MeHg may cause neurodevelopment impairment and potentially interfere with immune response, compromising proper control of neuroinflammation and aggravating neurodegeneration. Human populations are exposed to environmental contamination with MeHg, especially in areas with strong mining or industrial activity, raising public health concerns. Taking this into consideration, this work aims to clarify pathways leading to acute toxic effects caused by MeHg exposure in microglial cells. BV-2 mouse microglial cells were incubated with MeHg at different concentrations (0.01, 0.1, 1 and 10 µM) for 1 h prior to continuous Lipopolysaccharide (LPS, 0.5 µg/ml) exposure for 6 or 24 h. After cell exposure, reactive oxygen species (ROS), IL-6 and TNF-α cytokines production, inducible nitric oxide synthase (iNOS) expression, nitric oxide (NO) release, metabolic activity, propidium iodide (PI) uptake, caspase-3 and -9 activities and phagocytic activity were assessed. MeHg 10 µM decreased ROS formation, the production and secretion of pro-inflammatory cytokines IL-6, TNF-α, iNOS immunoreactivity, the release of NO in BV-2 cells. Furthermore, MeHg 10 µM decreased the metabolic activity of BV-2 and increased the number of PI-positive cells (necrotic-like cell death) when compared to the respective control group. Besides, MeHg did not interfere with caspase activity or the phagocytic profile of cells. The short-term effects of a high concentration of MeHg on BV-2 microglial cells lead to impaired production of several pro-inflammatory mediators, as well as a higher microglial cell death via necrosis, compromising their neuroinflammatory response. Clarifying the mechanisms underlying MeHg-induced neurotoxicity and neurodegeneration in brain cells is relevant to better understand acute and long-term chronic neuroinflammatory responses following MeHg exposure.

Contact dermatitis from black henna tattoo in child due to paraphenylenediamine

Temporary henna tattoos have become increasingly popular, particularly among children and teenagers. The word “henna” is of Persian origin, and it is prepared from the plant Lawsonia inermis belonging to the family Lythraceae. Concerning allergic reactions, natural henna paste is rarely responsible for contact dermatitis, which is more frequent if paraphenylenediamine (PPD) is added to the paste. The authors present a case of female child with erythematous exanthems that appeared after the application of black henna tattoo. A diagnosis of contact dermatitis to black henna tattoo was hypothesised. Epicutaneous tests were performed at the Immunoalergology Department of the Coimbra University Hospital using standard European battery and natural henna paste. The tests revealed positive reaction to PPD (AU)