Exploring the electronic structure of knotted proteins: the case of two ornithine transcarbamylase family.

CONTEXT: Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, so any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Using the electronic structure methods and quantum chemical descriptors analysis, we found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. In addition, we present a computationally feasible protocol, where we show it is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties. METHODS: In order to investigate these systems, we used PRIMoRDiA, a new software developed by our research group, to explore the electronic structure of biological macromolecules. We evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, belonging to the ornithine transcarbamylase family. We compared several sampled structures from these two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. The sampling was carried out through molecular dynamics simulations using ff14SB force field along 50 ns, and the semiempirical convergence was performed with PM7 Hamiltonian.

Pro- and Anti-inflammatory Biomarkers Responses after Aerobic Training in Heart Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND: Physical exercise (PE) may improve plasma concentration of interleukin- 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and adiponectin (adpN) in heart transplant (HT) patients. However, no consistent data is available on this population. AIM: Thus, we aimed to conduct a systematic review and meta-analysis on the effects of PE over these pro- and anti-inflammatory biomarkers in HT patients. METHODS: Following the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, we conducted a systematic literature search in the PubMed, Cochrane, and Scopus databases. Outcomes included IL-6, TNF-alpha, and adpN. Effect size (ES) was calculated using the standardized mean difference with a 95% confidence interval (CI). RESULTS: The PE group (aerobic modality) was associated with reduced IL-6 compared to the control group (ES: -0.53; 95% CI: -0.99 to -0.06 pg/mL; P = 0.026). However, the PE group did not show a significant effect on TNF-alpha and adpN levels (ES: -0.33; 95% CI: -0.79 to 0.13; P = 0.16 and ES: -0.20; 95% CI: -0.70 to 0.30 pg/mL; P = 0.444, respectively). CONCLUSION: PE is associated with IL-6 reductions, although TNF alpha and adpN did not change after this intervention in HT patients. Therefore, PE is an effective intervention to downregulate IL-6 in post-HT patients.

A multi-biomarker approach to verify chronic effects on Eisenia andrei earthworms exposed to tailings from one of the world's largest mining disasters.

Mining is of great relevance to the global economy, but its activities are challenging due to socio-environmental impacts. In January 2019, an iron ore tailings dam collapsed in Brumadinho (Minas Gerais, Brazil) releasing 12 × 106 m3 of tailings, causing human losses and devastation around 3.13 × 106 m2 of a watershed. In this context, the present study aimed to investigate the potential toxic effects of tailings from the collapsed dam using earthworms Eisenia andrei as a model organism for terrestrial environments. An extensive set of tests was performed, including behavioral (avoidance), acute (mortality and biomass) and chronic tests, such as biomass, reproduction and cytotoxicity (viability and cell density and change in coelomocyte pattern). The physical-chemical characterization revealed a higher density of the tailings in relation to the control soil, which can result in physical changes, such as soil compaction and surface sealing. Aluminum, Ca, Fe, Hg, Mg, Mn, K, Na and P registered higher concentrations in the tailings compared to the control soil, while Total Nitrogen, Total Organic Carbon and Organic Matter were higher in the natural soil. Based on the avoidance test, an EC50 of 27.18 ± 2.83% was estimated. No lethality was observed in the acute exposure, nor variations in biomass in the acute and chronic assays. However, there was a tendency to reduce the number of juveniles in relation to cocoons in the proportions of 3125; 12.5 and 25%. Significant changes in viability, cell density and pattern of amebocytes and eleocytes were observed up to the 35th day of exposure. A multi-biomarker approach (Integrated Biological Response version 2) indicated concentration-dependent effects and attenuation of cellular changes over time. These are the first results of chronic effects on earthworms exposed to tailings from the B1 dam. Despite being conclusive, we highlight the possible heterogeneity of the tailings and the necessary care in extrapolating the results.

Outlining the skin-homing and circulating CLA+NK cells in patients with severe atopic dermatitis.

Atopic dermatitis (AD) is a complex, multifactorial skin disease, characterized by pruritus and predominant Th2 inflammation. Innate immune cells may play a role in AD development and are composed of granulocytes, macrophages, innate-like T cells, and innate lymphoid cells. This study investigates the phenotypic and functional profile of circulating CLA+ natural killer (NK) cells and its role in the skin-homing to NK cells infiltrated in adults' skin with AD. We selected 44 AD patients and 27 non-AD volunteers for the study. The results showed increased frequencies of both CLA+CD56bright and CLA+CD56dim NK cell populations in the peripheral blood, mainly in severe AD patients. Upon SEB stimulation, we observed an augmented percentage of CLA+CD56dim NK cells expressing CD107a, IFN-γ, IL-10, and TNF, reinforcing the role of staphylococcal enterotoxins in AD pathogenesis. Additionally, we demonstrated increased dermal expression of both NK cell markers NCAM-1/CD56 and pan-granzyme, corroborating the skin-homing, mostly in severe AD. Further studies are necessary to elucidate the potential role of NK cells in the chronification of the inflammatory process in AD skin, as well as their possible relationship with staphylococcal enterotoxins, and as practicable therapeutic targets.

Physical-chemical influences and cell behavior of natural compounds on titanium dental surfaces.

The present study evaluated the influence of carvacrol, terpinene-4-ol, and chlorhexidine on the physical-chemical properties of titanium surfaces, cell viability, proliferation, adhesion, and spreading of fibroblasts and osteoblasts in vitro. Titanium surfaces (Ti) were treated with Carvacrol (Cvc), Terpinen-4-ol (T4ol), Chlorhexidine (CHX), DMSO, and ultrapure water (Control group). Physical-chemical modifications were evaluated by surface wettability, the surface free energy (SFE) calculated from the contact angle values using the Owens-Wendt-Rabel-Kaeble (OWRK) equation, scanning electron microscopy (SEM) and energy dispersive spectrometry probe (EDS) system. Cells were seeded onto Ti-treated surfaces and incubated for 24 h and 72 h, then evaluated by Alamar blue assay and fluorescence microscopy. Surfaces treated with Cvc and T4ol showed the presence of Na, O, and Cl. All surfaces showed hydrophilic characteristics and SFE values between 5.5 mN/m and 3.4 mN/m. On the other hand, EDS peaks demonstrated the presence of O and Cl after CHX treatment. A reduction of cell viability and adhesion was noted on titanium surfaces treated with CHX after 24 and 72h. In conclusion, the results indicate that the decontamination with Cvc and T4ol on Ti surfaces does not alter the surface proprieties and allows an adequate interaction with cells involved in the re-osseointegration process such as fibroblasts and osteoblasts.

[Integrative medicine and geriatrics : towards a convergence?] / Médecine intégrative et gériatrie : vers une convergence ?

In recent years integrative medicine has been the subject of growing interest among the overall population as well as the medical and scientific community. According to the Swiss health survey, approximately 40 % of the Swiss population regularly use complementary therapies. The fields of application of integrative medicine in geriatrics seem large (pain, cognitive disorders, end-of-life support, anxiety, etc.). Although scientific evidence is progressing in this area, studies targeting the population > 65 years old are still limited. The aim of this article is to expose some examples of complementary medicine applications in in geriatric care and the potential for rapprochement between integrative medicine and geriatric.

La médecine intégrative fait l'objet d'un intérêt accru au sein de la population et de la communauté médicale et scientifique ces dernières années. Selon l'Enquête suisse sur la santé, environ 40 % de la population suisse a régulièrement recours à des thérapies complémentaires. Les domaines d'application des médecines intégratives dans les soins gériatriques semblent vastes (douleurs, troubles du sommeil, accompagnement de fin de vie, anxiété, etc.). Les études ciblant spécifiquement la population de 65 ans et plus dans ce domaine restent encore limitées à notre connaissance. Cet article a pour but de présenter quelques exemples d'applications de médecine complémentaire dans la prise en charge des syndromes gériatriques et sensibiliser au potentiel de rapprochement entre la médecine intégrative et la gériatrie.

Improving Drug Delivery on Candida Albicans Using Geraniol Nanoemulsion.

Geraniol (GE) is a monoterpene alcohol with excellent antifungal activity. However, its low solubility and high volatility impair its use. Nanoemulsions (NE) are excellent delivery systems for poorly soluble and volatile drugs, achieving controlled release of the active ingredient. The aim of this study was to improve the delivery of geraniol (GE) incorporated in NE against Candida albicans in order to evaluate the antibiofilm effect and cytotoxicity. Nanoemulsion containing 10% oil phase (cholesterol) (w/w), 10% surfactant (mixture of soy phosphatidylcholine and Brij 58; 1:2) (w/w), and 80% aqueous phase (phosphate buffer) (w/w) was synthesized. Incorporation of GE was carried out by sonication and the final compounds were characterized by hydrodynamic diameter, polydispersity index (PDI), and zeta potential (ZP), in addition to evaluation of physicochemical stability after 6 months and 1 year. The GE-NE effect was evaluated on Candida albicans biofilms and cytotoxic effect was evaluated on immortalized normal oral cell line NOK-Si. The diameter of GE-NE was 232.3 ± 2.7 nm and PDI 0.155 with exhibited homogeneity and stability in solution. GE-NE showed antibiofilm activity at a concentration of 75 µg/mL with reduction of >6.0 log10, and no cytotoxicity against NOK-Si cells at concentrations below 150 µg/mL was observed. GE-NE proved to be a promising candidate for prevention and treatment of fungal diseases.

Physical-chemical influences and cell behavior of natural compounds on titanium dental surfaces

Abstract The present study evaluated the influence of carvacrol, terpinene-4-ol, and chlorhexidine on the physical-chemical properties of titanium surfaces, cell viability, proliferation, adhesion, and spreading of fibroblasts and osteoblasts in vitro. Titanium surfaces (Ti) were treated with Carvacrol (Cvc), Terpinen-4-ol (T4ol), Chlorhexidine (CHX), DMSO, and ultrapure water (Control group). Physical-chemical modifications were evaluated by surface wettability, the surface free energy (SFE) calculated from the contact angle values using the Owens-Wendt-Rabel-Kaeble (OWRK) equation, scanning electron microscopy (SEM) and energy dispersive spectrometry probe (EDS) system. Cells were seeded onto Ti-treated surfaces and incubated for 24 h and 72 h, then evaluated by Alamar blue assay and fluorescence microscopy. Surfaces treated with Cvc and T4ol showed the presence of Na, O, and Cl. All surfaces showed hydrophilic characteristics and SFE values between 5.5 mN/m and 3.4 mN/m. On the other hand, EDS peaks demonstrated the presence of O and Cl after CHX treatment. A reduction of cell viability and adhesion was noted on titanium surfaces treated with CHX after 24 and 72h. In conclusion, the results indicate that the decontamination with Cvc and T4ol on Ti surfaces does not alter the surface proprieties and allows an adequate interaction with cells involved in the re-osseointegration process such as fibroblasts and osteoblasts.

Resumo O presente estudo avaliou a influência do carvacrol, terpineno-4-ol e clorexidina nas propriedades físico-químicas de superfícies de titânio, viabilidade celular, proliferação, adesão e esplhamento de fibroblastos e osteoblastos in vitro. Superfícies de titânio (Ti) foram tratadas com Carvacrol (Cvc), Terpinen-4-ol (T4ol), Clorexidina (CHX), DMSO e água ultrapura (Grupo Controle). As modificações físico-químicas foram avaliadas pela molhabilidade da superfície, a energia livre de superfície (ELS) calculada a partir dos valores do ângulo de contato usando a equação de Owens-Wendt-Rabel-Kaeble (OWRK), microscopia eletrônica de varredura (MEV) e espectroscopia de raios X por energia dispersiva (EDS). As células foram semeadas em superfícies tratadas com Ti e incubadas por 24 h e 72 h, e avaliadas pelo ensaio Alamar blue e microscopia de fluorescência. As superfícies tratadas com Cvc e T4ol mostraram a presença de Na, O e Cl. Todas as superfícies apresentaram características hidrofílicas e valores de ELS entre 5,5 mN/m e 3,4 mN/m. Por outro lado, os picos de EDS demonstraram a presença de O e Cl após o tratamento com CHX. Uma redução da viabilidade celular e adesão foi observada em superfícies de titânio tratadas com CHX após 24 e 72h. Em conclusão, os resultados indicam que a descontaminação com Cvc e T4ol em superfícies de Ti não altera as propriedades da superfície e permite uma interação adequada com células envolvidas no processo de reosseointegração como fibroblastos e osteoblastos.

Homologue Composition of Technical Chlorinated Paraffins Used in Several Countries over the Last 50 Years─SCCPs Are Still Out There.

Chlorinated paraffins (CPs) are widely produced chemicals, with certain CP subgroups facing global restrictions due to their environmental dispersion, persistence, bioaccumulation, and toxicity. To evaluate the effectiveness of these international restrictions, we assessed the homologue group contribution and the mass fraction of short-chain CPs (SCCPs: C10-C13), medium-chain CPs (MCCPs: C14-C17), and long-chain CPs (LCCPs: ≥C18) in 36 technical CP mixtures used worldwide over the last 50 years. Using low-resolution mass spectrometry (LC-ESI-MS/MS), we quantified 74 CP homologue groups (C10Cl4-C20Cl10). Additionally, high-resolution mass spectrometry (LC-ESI-QTOF-MS) screening was employed to identify unresolved CP contents, covering 375 CP homologue groups (C6Cl4-C30Cl30). Overall, 1 sample was mainly composed of

Chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion enhances photodynamic therapy against multi-species biofilms related to periodontitis.

In our previous studies, Chlorin-e6 (Ce6) demonstrated a significant reduction of microorganisms' viability against multi-species biofilm related to periodontitis while irradiated with blue light. However, the conjugation of Ce6 and antimicrobial peptides, and the incorporation of this photosensitizer in a nanocarrier, is still poorly explored. We hypothesized that chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion could inhibit a multi-species biofilm related to periodontitis during photodynamic therapy (PDT), the pre-treatment with hydrogen peroxide was also tested. The nanoemulsion (NE) incorporated with Ce6 was characterized regarding the physiochemical parameters. Images were obtained by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Later, the Ce6 and LL-37 incorporated in NE was submitted to UV-Vis analysis and Reactive Oxygen Species (ROS) assay. Finally, the combined formulation (Ce6+LL-37 in nanoemulsion) was tested against multi-species biofilm related to periodontitis. The formed nanoformulation was kinetically stable, optically transparent with a relatively small droplet diameter (134.2 unloaded and 146.9 loaded), and weak light scattering. The NE system did not impact the standard UV-VIS spectra of Ce6, and the ROS production was improved while Ce6 was incorporated in the NE. The combination of Ce6 and LL-37 in NE was effective to reduce the viability of all bacteria tested. The treatment with hydrogen peroxide previous to PDT significantly impacted bacterial viability. The current aPDT regimen was the best already tested against periodontal biofilm by our research team. Our results suggest that this combined protocol must be exploited for clinical applications in localized infections such as periodontal disease. - Nanoemulsion demonstrated to be an excellent nanocarrier for photodynamic application. - Chlorin-e6 incorporated in nanoemulsion showed great physicochemical and biophotonic parameters. - The combination of chlorin-e6 and LL-37 peptide in nanoemulsion is effective to eliminate periodontal pathogenic bacteria. - The treatment with hydrogen peroxide previous to PDT significantly impacted bacterial viability.

First assessment of atmospheric pollution by trace elements and particulate matter after a severe collapse of a tailings dam, Minas Gerais, Brazil: An insight into biomonitoring with Tillandsia usneoides and a public health dataset.

In this study, samples of bromeliad Tillandsia usneoides (n = 70) were transplanted and exposed for 15 and 45 days in 35 outdoor residential areas in Brumadinho (Minas Gerais state, Brazil) after one of the most severe mining dam collapses in the world. Trace elements aluminum (Al), arsenic (As), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), nickel (Ni) and zinc (Zn) were quantified by atomic absorption spectrometry. Scanning electron microscope generated surface images of T. usneoides fragments and particulate matter (PM2.5, PM10 and PM > 10). Aluminum, Fe and Mn stood out from the other elements reflecting the regional geological background. Median concentrations in mg kg-1 increased (p < 0.05) between 15 and 45 days for Cr (0.75), Cu (1.23), Fe (474) and Mn (38.1), while Hg (0.18) was higher at 15 days. The exposed-to-control ratio revealed that As and Hg increased 18.1 and 9.4-fold, respectively, not showing a pattern associated only with the most impacted sites. The PM analysis points to a possible influence of the prevailing west wind on the increase of total particles, PM2.5 and PM10 in transplant sites located to the east. Brazilian public health dataset revealed increase in cases of some cardiovascular and respiratory diseases/symptoms in Brumadinho in the year of the dam collapse (1.38 cases per 1000 inhabitants), while Belo Horizonte capital and its metropolitan region recorded 0.97 and 0.37 cases, respectively. Although many studies have been carried out to assess the consequences of the tailings dam failure, until now atmospheric pollution had not yet been evaluated. Furthermore, based on our exploratory analysis of human health dataset, epidemiological studies are required to verify possible risk factors associated with the increase in hospital admissions in the study area.

Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review.

Ongoing research explores the underlying causes of ulcerative colitis and Crohn's disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term "microbiota" pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1ß. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1ß, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.

Quantum chemical descriptors based on semiempirical methods for large biomolecules.

In this Review, we reviewed the efforts to expand the applications of conceptual density functional theory reactivity descriptors and hard and soft acid and base principles for macromolecules and other strategies that focused on low-level quantum chemistry methods. Currently, recent applications are taking advantage of modifications of these descriptors using semiempirical electronic structures to explain enzymatic catalysis reactions, protein-binding processes, and structural analysis in proteins. We have explored these new solutions along with their implementations in the software PRIMoRDiA, discussing their impact on the field and its perspectives. We show the main issues in the analysis of the electronic structure of macromolecules, which are the application of the same calculation protocols used for small molecules without considering particularities in those large systems' electronic configuration. The major result of our discussions is that the use of semiempirical methods is crucial to obtain such a type of analysis, which can provide a powerful dimension of information and be part of future low-cost predictive tools. We expect semiempirical methods continue playing an important role in the quantum chemistry evaluation of large molecules. As computational resources advance, semiempirical methods might lead us to explore the electronic structure of even larger biological macromolecular entities and sets of structures representing larger timescales.

Efficacy of six exercise-based interventions for individuals undergoing hemodialysis: a network meta-analysis of randomized clinical trials.

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.

Employment and gender inequalities: Towards a more cohesive and gender-neutral transport sector in Portugal.

BACKGROUND: Historically, the transport sector has been male-dominated in all countries, including Portugal. In recent years, Portugal has struggled to balance the proportion of men and women working in the transport sector through policies, programs, and awareness campaigns. In most cases, the overall impact has been rather unsatisfactory, questioning the necessity of introducing other methods and strategies. OBJECTIVE: The main objectives were to assess the existing gender inequalities in the Portuguese transport sector labour market, identify the causes, and propose guidelines and possible solutions towards a more inclusive and gender-neutral society. METHODS: Using both qualitative and quantitative methods, the methodological background of this research is divided into three main parts: (i) a literature review of academic publications, reports, and laws in the European and Portuguese context, (ii) semi-structured interviews with representatives of two Portuguese transport companies, and (iii) statistical analysis compiling data from European and national official sources. RESULTS: There is evidence of differences in opportunities between women and men, starting with lower mobility and access to the labour market. Some companies in the sector have already recognised the existence of asymmetries and have introduced policies and measures to reduce them. Nonetheless, the actions already implemented have not led to the expected results. CONCLUSION: More governmental and institutional attention should be provided to develop gender-neutral employment policies for the transport sector and more accurate gender equality measures and instruments to change the status quo are needed. This paper presents a series of recommendations for better governance of gender inequalities in the Portuguese transport labour market.

Effects of intradialytic inspiratory muscle training at different intensities on diaphragm thickness and functional capacity: clinical trial protocol in patients undergoing haemodialysis.

INTRODUCTION: Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) commonly present with a sedentary behaviour and reduced functional capacity, factors that can compromise their prognosis. Intradialytic inspiratory muscle training (IMT) can increase respiratory muscle strength and, consequently, improve functional capacity, besides being easy to apply, cheap and performed in a supervised setting. However, few studies show the effects of this type of training applied at different intensities in this population. This study aims to compare the effects of IMT at different intensities in adults with ESRD undergoing HD. METHODS AND ANALYSIS: A randomised, double-blind, sham-controlled trial will be conducted on 36 subjects randomly allocated into three groups: IMT at intensities of 30% or 50% of maximal inspiratory pressure (intervention groups), or 10% of maximal inspiratory pressure (sham-IMT). All the interventions will be supervised and performed three times per week, for 12 weeks, totalling 36 sessions. The primary outcomes are the 6-minute walk test, diaphragm thickness and the response of VO2peak post-intervention. Respiratory muscle strength, 24-hour ambulatory blood pressure measurement and the Kidney Disease Quality of Life 36-item short form survey will be evaluated as secondary outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (ID: 2020-0458). The results of this study will be disseminated by conference presentations and peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04660383.

Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review.

Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR's numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR's solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.

Guillain-Barré syndrome associated with COVID-19: A systematic review.

With the outbreak of coronavirus disease 2019 (COVID-19), the whole world was impacted by a pandemic. With the passage of time and knowledge about the dynamics and viral propagation of this disease, the short-, medium- and long-term repercussions are still being discovered. During this period, it has been learned that various manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the nervous system. In recent months, a variety of studies and case reports have proposed an association between COVID-19 and Guillain-Barré syndrome (GBS). The present work aims to systematically review the publications available to date to verify the relationship between these two pathologies and the characteristics of post-COVID GBS. There were 156 studies included in this work, resulting in a total of 436 patients. The findings show a mean age of the patients of 61,38 years and a male majority. The GBS symptoms began on average 19 days after the onset of COVID-19 infection. Regarding GBS, the main manifestations found included generalized weakness, reflex reduction, facial paresis/paralysis and hypoesthesia. As expected, the most common result in cerebrospinal fluid (CSF) analysis was albuminocytological dissociation. A pattern of blood analysis findings common to all patients was not observed due to non-standardization of case reports. Regarding electrodiagnostic studies, acute inflammatory demyelinating polyneuropathy (AIDP) appeared as the most common subtype of GBS in this study. There have been reports, to a lesser extent, of acute motor axonal neuropathy (AMAN), acute sensorimotor axonal neuropathy (AMSAN), the pharyngeal-cervical-brachial variant (PCB), and Miller-Fisher syndrome (MFS). The GBS treatment used was mainly intravenous immunoglobulin (IVIG) and plasma exchange (PLEX). Therefore, the present study reports a high prevalence of hospitalization and intensive care units ICU admissions, conjecturing a relationship between the development of GBS and the severity of COVID-19. Despite the severity, most patients showed improvement in GBS symptoms after treatment, and their residual symptoms did not include motor involvement. Therefore, the development of GBS seems to be related to COVID-19 infection, as reported by the present systematic review.

Chlorin-based photosensitizer under blue or red-light irradiation against multi-species biofilms related to periodontitis.

In our previous study, Chlorin-e6 (Ce6) demonstrated a significant reduction of microorganisms' viability against single-species biofilm related to periodontitis once irradiated by red light (660 nm). Also, higher bacteria elimination was observed under blue light (450 nm) irradiation. However, the use of blue light irradiation of Ce6 for antimicrobial administration is poorly explored. This study evaluated the effect of chlorin-e6-mediated antimicrobial photodynamic therapy (aPDT) using different wavelengths (450 or 660 nm) against multi-species biofilms related to periodontitis. Streptococcus oralis, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans composed the mature biofilm developed under proper conditions for five days. aPDT was performed using different concentrations of Ce6 (100 and 200 µM), wavelengths (450 or 660 nm), and comparisons were made after qPCR assay and confocal laser scanning microscopy (CLSM) analysis. The greatest bacterial elimination was observed in the groups where Ce6 was used with blue light, for S. orallis (2.05 Log10 GeQ mL-1, p < 0.0001) and P. gingivalis (1.4 Log10 GeQ mL-1, p < 0.0001), aPDT with red light showed significant bacteria reduction only for S. orallis. aPDT with blue light demonstrated statistically higher elimination in comparison with aPDT with red light. The aPDT did not show a statistically significant effect when tested against A. actinomycetemcomitans and F. nucleatum (p=0.776 and 0.988, respectively). The aPDT using blue light showed a promising higher photobiological effect, encouraging researchers to consider it in the irradiation of Ce6 for further investigations.