ABSTRACT
Disasters are defined as unpredictable and complex situations. This theoretical-reflective study, conducted from August 2020 to December 2020, reflected on occupational nursing during disasters in light of Myra Levine's holistic theory. The first principle of her model is to conserve human energy, focusing on vital sign measurement; the second, conservation of structural integrity, focuses on multiple injuries; the third, conservation of personal integrity, focuses on relationships; while the fourth, conservation of social integrity, involves public and private dimensions beyond an individual level. Levine's conservation model is of special utility in disaster situations, since it is rooted in occupational nursing care, working toward effective adaptation of nursing processes for individuals and families, aiming to achieve professional autonomy and quality care for patients, their families, and society.
Os desastres caracterizam-se como situações imprevisíveis e complexas. Este artigo objetivou refletir sobre a ótica da enfermagem do trabalho em desastres, fundamentada na teoria holística de Myra Estrin Levine. Trata-se de um estudo teóricoreflexivo desenvolvido no período de agosto a dezembro de 2020. Na teoria holística, o primeiro princípio é a conservação da energia do ser humano, com foco na medida dos sinais vitais. Já a conservação da integridade estrutural foca nas experiências múltiplas com lesões. A conservação da integridade pessoal se refere aos relacionamentos para definirem a si mesmos. Por fim, a conservação da integridade social, por sua vez, envolve a definição do ser que vai além do indivíduo e possui dimensões pública e particular. O modelo holístico de Myra Estrin Levine contribui em especial com a temática de desastres, tendo em vista que, ancorada no cuidado de enfermagem no contexto ocupacional, baseia-se em trabalhar de forma didática a adaptação eficaz do processo de enfermagem aos indivíduos e às famílias, além de contribuir com o processo de enfermagem, visando alcançar a autonomia profissional e a boa qualidade da assistência prestada ao cliente, à família e à sociedade.
ABSTRACT
Quilombo remnant communities are areas officially recognized by the Brazilian government as historical communities founded by formerly enslaved individuals. These communities are mostly located in the endemic areas of malaria in the Brazilian Amazon. We retrospectively described the prevalence of malaria among individuals living in 32 recognized quilombo remnant communities in the Baiao and Oriximina municipalities located in the Para State. The number of malaria cases and the Annual Parasitic Incidence (API) recorded by the Brazilian malaria surveillance system (SIVEP-Malaria) from January 2005 to December 2020 were analyzed. We found that all communities registered at least one case over the 16-year period, the most frequent parasitic species being Plasmodium vivax (76.1%). During this period, 0.44% (4,470/1,008,714) of the malaria cases registered in Para State were reported in these quilombo remnant communities, with frequencies of 10.9% (856/7,859) in Baiao municipality and 39.1% (3,614/9,238) in Oriximina municipality, showing that individuals living in these rural communities are exposed to malaria. These data indicate that effective surveillance requires improved measures to identify malaria transmission among vulnerable populations living in quilombo remnant communities in the Brazilian Amazon.
Subject(s)
Malaria, Vivax , Vulnerable Populations , Humans , Brazil/epidemiology , Cross-Sectional Studies , Retrospective Studies , Prevalence , Malaria, Vivax/epidemiology , Incidence , Female , Male , Adult , Rural Population , Adolescent , Malaria/epidemiology , Malaria/transmission , Young Adult , Child , Middle Aged , Malaria, Falciparum/epidemiology , Child, PreschoolABSTRACT
OBJECTIVES: The objective of this systematic review and meta-analysis is to evaluate the influence of caffeine (CAF) intake strategies, taking into account their form, timing, and dosage, on heart rate variability (HRV) indices in the post-exercise recovery period. METHODS: The meta-analysis adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and is registered in the PROSPERO database (CRD42023425885). A comprehensive literature search was carried out across MEDLINE, Web of Science, LILACS, and SCOPUS, concluding in May 2023. We concentrated on randomized clinical trials comparing CAF supplementation effects to placebo on HRV indices post-exercise in active adults aged 18 and above. The primary endpoint was the assessment of HRV indices, measured both prior to and following exercise. RESULTS: Of the 10 studies included, 7 were used for the meta-analysis, and all contributed to the systematic review. The research explored a variety of CAF strategies, spanning different forms (capsule, drink, gum), times (10, 45, 60 min) and doses (2.1 to 6.0 mg/kg). The outcomes revealed no substantial variations between the placebo and CAF conditions in terms of both the square root of the average of successive squared differences between adjacent RR intervals (RMSSD) (standardized mean difference (SMD) -0.03, 95% CI -0.265 to 0.197, p=0.77) and high frequency (HF) index (SMD -0.061, 95% CI -0.272 to 0.150, p=0.57). Furthermore, metaregression analysis, employing a fixed-effects model and accounting for the administered CAF doses, revealed no significant correlation between caffeine doses and HRV indices (p>0.05). CONCLUSION: In conclusion, there is moderate-certainty evidence suggesting that different CAF intake strategies, encompassing aspects such as form, time, and dose, do not have a significant impact on HRV indices recovery post-exercise (i.e., vagal modulation).
Subject(s)
Caffeine , Exercise , Heart Rate , Humans , Caffeine/administration & dosage , Heart Rate/physiology , Heart Rate/drug effects , Exercise/physiology , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/pharmacology , Recovery of Function , Post-Exercise RecoveryABSTRACT
Albeit one of the most pervasive forms of gender violence, street harassment tends to be either not considered a crime or to be faulty criminalized. This investigation contributes to better understand the overall inefficiency of existing laws through an analysis of the criminalization of street harassment in Portugal. Particularly, it searches for obstacles to implementation among those responsible for the process-the street-level bureaucrats of the Portuguese Public Security Police. Through 14 semi-structured interviews, three groups of obstacles to implementation were identified: perceptions of the legislation's content, a masculinist institutional culture, and personal characteristics. These are new findings that contribute to an understanding of the perpetuation of gender violence through state's institutions and workers.
Subject(s)
Sexual Harassment , Violence , Male , Humans , Portugal , Crime , PoliceABSTRACT
Stimulating CT-afferents by forearm caresses produces the subjective experience of pleasantness in the receiver and modulates subjective evaluations of viewed affective images. Receiving touch from another person includes the social element of another person's presence, which has been found to influence affective image evaluations without involving touch. The current study investigated whether these modulations translate to facial muscle responses associated with positive and negative affect across touch-involving and mere presence conditions. Female participants (N = 40, M(age) = 22.4, SD = 5.3) watched affective images (neutral, positive, negative) while facial electromyography was recorded (sites: zygomaticus, corrugator). Results from ANOVAs showed that providing touch to another person or oneself modulated zygomaticus site responses when viewing positive images. Providing CT-afferent stimulating touch (i.e., forearm caresses) to another person or oneself dampened the positive affective facial muscle response to positive affective images. Providing touch to another person generally increased corrugator facial muscle activity related to negative affect. Receiving touch did not modulate affective facial muscle responses during the viewing of affective images but may have effects on later cognitive processes. Together, previously reported social and touch modulations of subjective evaluations of affective images do not translate to facial muscle responses during affective image viewing, which were differentially modulated.
Subject(s)
Touch Perception , Touch , Humans , Female , Young Adult , Adult , Touch/physiology , Facial Muscles/physiology , Touch Perception/physiology , Emotions/physiology , Face/physiology , ElectromyographyABSTRACT
Ketamine is an anesthetic drug that also has antidepressant properties, with quick action. Despite the great number of studies showing its effectiveness as a treatment for major depression, there is little information about its effects on postpartum depression, as pharmacological treatments bring risks to the health of both mother and child. Thus, this study aimed to evaluate the effects of prolonged treatment with subanesthetic doses of ketamine in a rat model of postpartum depression. Female dams were induced to postpartum depression by the maternal separation model from lactating day (LD) 2-12. They were divided into four groups: one control and three experimental groups, which were treated with different doses of ketamine (5, 10 or 20 mg/kg) from LD 2-21 i.p. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day 2 through 90. Ketamine causes poor maternal care, with few neurochemical alterations. However, the highest dose used in this study had an antidepressant effect. Regarding the male offspring, indirect exposure to ketamine through breast milk caused few behavioral changes during infancy, but they were not permanent, as they faded in adulthood. Nevertheless, this exposure was able to cause alterations in their monoaminergic neurotransmission systems that were found in both infancy and adulthood periods.
Subject(s)
Depression, Postpartum , Depressive Disorder, Major , Ketamine , Humans , Child , Rats , Male , Animals , Female , Depression, Postpartum/drug therapy , Lactation , Maternal Deprivation , Depression/drug therapy , Antidepressive Agents , Depressive Disorder, Major/drug therapyABSTRACT
ABSTRACT Quilombo remnant communities are areas officially recognized by the Brazilian government as historical communities founded by formerly enslaved individuals. These communities are mostly located in the endemic areas of malaria in the Brazilian Amazon. We retrospectively described the prevalence of malaria among individuals living in 32 recognized quilombo remnant communities in the Baiao and Oriximina municipalities located in the Para State. The number of malaria cases and the Annual Parasitic Incidence (API) recorded by the Brazilian malaria surveillance system (SIVEP-Malaria) from January 2005 to December 2020 were analyzed. We found that all communities registered at least one case over the 16-year period, the most frequent parasitic species being Plasmodium vivax (76.1%). During this period, 0.44% (4,470/1,008,714) of the malaria cases registered in Para State were reported in these quilombo remnant communities, with frequencies of 10.9% (856/7,859) in Baiao municipality and 39.1% (3,614/9,238) in Oriximina municipality, showing that individuals living in these rural communities are exposed to malaria. These data indicate that effective surveillance requires improved measures to identify malaria transmission among vulnerable populations living in quilombo remnant communities in the Brazilian Amazon.
ABSTRACT
ABSTRACT Objectives: to synthesize research on factors associated with Burnout Syndrome (BS) in police officers. Methods: a scoping review was conducted without temporal or language restrictions. Data were exported to EndNote to remove duplicates and then imported into the Rayyan app for organization, article selection, and data extraction. Results: a total of 4559 publications were identified, with 50 studies included in the review. Research conducted in Brazil and the United States predominated. Certain occupational factors were found to be more closely linked to police officers compared to other professions, including law enforcement, frequency of interaction with suspects and criminals, rank, dissatisfaction with the organization, and civilian confrontations. Conclusions: certain aspects of the police profession contribute to BS, even in countries with better working conditions in public security. It is recommended to prioritize health promotion initiatives for these professionals.
RESUMEN Objetivos: sintetizar los estudios que abordan los factores asociados al síndrome de burnout (SB) en policías. Métodos: revisión de alcance, sin restricción temporal y de idiomas con exportación a EndNote, eliminación de duplicados y exportación a la aplicación Rayyan para organización, selección de artículos y extracción de datos. Resultados: se identificaron 4559 publicaciones con inclusión de 50 estudios. Hubo predominio de investigaciones realizadas en Brasil y Estados Unidos. Algunos factores laborales estuvieron más relacionados con los policías en comparación con otras profesiones, como la aplicación de la ley, la frecuencia de interacción con sospechosos y criminales, ser cabo, insatisfacción con la corporación y enfrentamientos con civiles. Conclusiones: ciertos aspectos laborales contribuyen al SB, incluso en países con mejores condiciones laborales en Seguridad Pública. Se recomienda priorizar acciones de promoción de la salud para estos profesionales.
RESUMO Objetivos: sintetizar os estudos que abordam os fatores associados à síndrome de burnout (SB) em policiais. Métodos: revisão de escopo, sem restrição temporal e de idiomas, com exportação para o EndNote, suprimindo os duplicados, e exportados para o aplicativo Rayyan, para organização, seleção dos artigos e extração dos dados. Resultados: foram identificadas 4559 publicações, com inclusão de 50 estudos. Houve predominância de pesquisas realizadas no Brasil e nos Estados Unidos. Alguns fatores laborais foram mais relacionados aos policiais quando comparados com outras profissões, como a aplicação da lei, frequência de interação com suspeitos e criminosos, ser cabo, insatisfação com a corporação e confrontos com civis. Conclusões: certos aspectos laborais contribuem para a SB, mesmo em países com melhores condições de trabalho na Segurança Pública. Recomenda-se priorizar ações de promoção da saúde para esses profissionais.
ABSTRACT
This study aims to evaluate if the relation between love life satisfaction, assessed by the satisfaction with love life scale (SWLLS), and capacity to love, assessed by the capacity to love inventory (CTL-I), is moderated by gender and by being or not in a romantic relationship, in a Portuguese sample. To this end, the adaptation and validation of CTL-I for this population were carried out through an exploratory factorial analysis (EFA) followed by a Robust Maximum Likelihood (MLR) confirmatory factorial analysis (CFA). A multi-group analysis for measurement invariance depending on being in a romantic relationship or not was assessed. The model's reliability was also evaluated. The associations between SWLLS and CTL-I were tested by correlations, regressions and moderations. At last, differences between means and distributions concerning sociodemographic variables were determined. The results showed that a good model fit for the Portuguese version of the CTL-I was found, as well as good psychometric properties. Results also showed that satisfaction with love life contributes to explaining the capacity to love and all its dimensions, and that gender and being in a romantic relationship moderate the association between love life satisfaction and the capacity to love. Being female and being in a romantic relationship make the relationship between love life satisfaction and the capacity to love stronger and more meaningful.
Subject(s)
Interpersonal Relations , Love , Humans , Female , Male , Reproducibility of Results , Personal Satisfaction , PsychometricsABSTRACT
The plant-specific family of GRAS transcription factors has been wide implicated in the regulation of transcriptional reprogramming associated with a diversity of biological functions ranging from plant development processes to stress responses. Functional analyses of GRAS transcription factors supported by in silico structural and comparative analyses are emerging and clarifying the regulatory networks associated with their biological roles. In this review, a detailed analysis of GRAS proteins' structure and biochemical features as revealed by recent discoveries indicated how these characteristics may impact subcellular location, molecular mechanisms, and function. Nomenclature issues associated with GRAS classification into different subfamilies in diverse plant species even in the presence of robust genomic resources are discussed, in particular how it affects assumptions of biological function. Insights into the mechanisms driving evolution of this gene family and how genetic and epigenetic regulation of GRAS contributes to subfunctionalization are provided. Finally, this review debates challenges and future perspectives on the application of this complex but promising gene family for crop improvement to cope with challenges of environmental transition.
ABSTRACT
Graphene oxide (GOX) has become attractive due to its unique physicochemical properties. This nanomaterial can associate with other dendrimers, making them more soluble and allowing better interaction with biomacromolecules. The present study aimed to investigate, by real-time microscopy, the behavior of human breast cancer cells exposed to particles of materials based on graphene oxide. The MCF-7 cell line was exposed to GOX, GOX associated with Polypropylenimine hexadecaamine Dendrimer, Generation 3.0-DAB-AM-16 (GOXD) and GOX associated with polypropyleneimine-PAMAM (GOXP) in the presence or absence of fetal bovine serum (FBS). GOX, GOXD and GOXP were taken up by the cells in clusters and then the clusters were fragmented into smaller ones inside the cells. Real-time microscopy showed that the presence of FBS in the culture medium could allow a more efficient internalization of graphene materials. After internalizing the materials, cells can redistribute the clumps to their daughter cells. In conclusion, the present study showed that the particles can adhere to the cell surface, favoring their internalization. The presence of FBS contributed to the formation of smaller aggregates of particles, avoiding the formation of large ones, and thus transmitted a more efficient internalization of the materials through the interaction of the particles with the cell membrane.
ABSTRACT
Zika virus infection is associated to severe diseases such as congenital microcephaly and Zika fever causing serious harm to humans and special concern to health systems in low-income countries. Currently, there are no approved drugs against the virus, and the development of anti-Zika virus drugs is thus urgent. The present investigation describes the discovery and hit expansion of a N-acyl-2-aminobenzothiazole series of compounds against Zika virus replication. A structure-activity relationship study was obtained with the synthesis and evaluation of anti-Zika virus activity and cytotoxicity on Vero cells of nineteen derivatives. The three optimized compounds were 2.2-fold more potent than the initial hit and 20.9, 7.7 and 6.4-fold more selective. Subsequent phenotypic and biochemical assays were performed to evidence whether non-structural proteins, such as the complex NS2B-NS3pro, are related to the mechanism of action of the most active compounds.
Subject(s)
Zika Virus Infection , Zika Virus , Animals , Chlorocebus aethiops , Humans , Vero Cells , Zika Virus Infection/drug therapy , Structure-Activity Relationship , Virus Replication , Antiviral Agents/chemistry , Viral Nonstructural ProteinsABSTRACT
The NS2B-NS3 protease (NS2B-NS3pro) is regarded as an interesting molecular target for drug design, discovery, and development because of its essential role in the Zika virus (ZIKV) cycle. Although no NS2B-NS3pro inhibitors have reached clinical trials, the employment of drug-like scaffolds can facilitate the screening process for new compounds. In this study, we performed a combination of ligand-based and structure-based in silico methods targeting two known non-peptide small-molecule scaffolds with micromolar inhibitory activity against ZIKV NS2B-NS3pro by a virtual screening (VS) of promising compounds. Based on these two scaffolds, we selected 13 compounds from an initial library of 509 compounds from ZINC15's similarity search. These compounds exhibited structural modifications that are distinct from previously known compounds yet keep pertinent features for binding. Despite promising outcomes from molecular docking and initial enzymatic assays against NS2B-NS3pro, confirmatory assays with a counter-screening enzyme revealed an artifactual inhibition of the assessed compounds. However, we report two compounds, 9 and 11, that exhibited antiviral properties at a concentration of 50 µM in cellular-based assays. Overall, this study provides valuable insights into the ongoing research on anti-ZIKV compounds to facilitate and improve the development of new inhibitors.
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Fungal pigments, including melanin, are recognized as promising materials for biomedical, environmental, and technological applications. In previous studies, we have demonstrated that the DOPA-melanin produced by the MEL1 mutant of Aspergillus nidulans exhibits antioxidant, anti-inflammatory, and antimicrobial activities without any cytotoxic or mutagenic effects, suggesting its potential use in pharmaceuticals. In order to increase the yield of this pigment and reduce the costs of its large-scale production, the present study aimed to evaluate agro-industrial by-products, sugarcane molasses, vinasse, and corn steep liquor as inexpensive substrates for fungal growth using experimental design methodology. According to the results obtained, the optimal composition of the culture medium was 0.81% (v/v) vinasse and 1.62% (w/v) glucose, which promoted a greater production of melanin (225.39 ± 4.52 mg g-1 of biomass), representing a 2.25-fold increase compared with the condition before optimization (100.32 mg.g-1 of biomass). Considering the amount of biomass obtained in the optimized condition, it was possible to obtain a total melanin production of 1 g L-1. Therefore, this formulation of a less complex and low-cost culture medium composition makes the large-scale process economically viable for future biotechnological applications of melanin produced by A. nidulans.
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Interest in products with more natural ingredients increases the potential for application of Biosurfactants in foods. The aim of the present study was to assess the toxicity of biosurfactant produced by Saccharomyces cerevisiae URM6670 and the effect of the incorporation of this biosurfactant on the physicochemical and textural characteristics of cookies and muffins, performing unprecedented assessment of the sensorial effects of this application. The toxicity analysis revealed that the biosurfactant is classified as a mild irritant, with irritation indices lower than 4.9. The physical analysis of the incorporation of the biosurfactant in the formulation revealed that the addition of 1% to cookies significantly increased the diameter and spread factor. In muffins, significant changes in these properties were found beginning at 0.25% biosurfactant. The moisture content in cookies was reduced by a maximum of 74%, while in muffins this reduction was approximately 6%. The lipid content increased significantly with the addition of 1% of the biosurfactant (11% in cookies and 25% in muffins). The textural analysis revealed that the biosurfactant at 1% led to a significant increase in firmness as a consequence of the reduction in the moisture content. In muffins, the same concentration increased the firmness and variables related to chewability. The sensory analysis revealed that the muffins with biosurfactant had greater acceptance compared to the cookies. Thus, the biosurfactant demonstrated potential application in bakery products due to low toxicity and positive evaluation in important sensorial parameters for its commercialisation.
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Abstract Background Self-care in the management of systemic arterial hypertension (SAH) is crucial, and validated instruments can help researchers and health professionals to plan strategies to improve self-care in people with SAH. Objective The main objective of this study was to translate, cross-culturally adapt, and validated the Hypertension Self-Care Profile (HBP-SCP) for Brazilian Portuguese. Methods The translation and cross-cultural adaptation was performed in five phases, and the pre-final version was tested in 30 individuals, native speakers of Portuguese with a diagnosis of hypertension. The final version was administered in 100 individuals. The inclusion criteria were: diagnosis of SAH, characterized by systolic arterial blood pressure ≥ 140 mmHg and/or diastolic arterial blood pressure ≥ 90mmHg, regular use of antihypertensive medications and over 18 years of age. The present study also used two other questionnaires, previously validated for the Brazilian population, to verify the validity of the construct, the Healthy Habits Perception Questionnaire (HHPQ) and the Quality of Life in Hypertension Mini-Questionnaire (MINICHAL-BRASIL). Results During the translation and cross-cultural adaptation phase, there were no disagreements. Adequate reliability — intraclass correlation coefficient (ICC) ≥ 0.89, standard error of measurement (SEM) % ≤ 4.34, minimum detectable change (MDC) % ≤ 12.04 — and internal consistency (Cronbach's alpha ≥ 0.75) were observed. The behavior domain of HBP-SCP obtained significant correlations (p < 0.05) with the self-efficacy domain and HHPQ; the motivation domain with the self-efficacy domain; and the self-efficacy domain with the somatic manifestation domain of MINICHAL-BRASIL. No ceiling and floor effects were observed. Conclusions The Brazilian Portuguese version of the HBP-SCP has adequate psychometric properties, according to the best scientific recommendations.
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BACKGROUND: Rosacea prevalence varies worldwide and there is a lack of information in Brazil. OBJECTIVES: To describe the epidemiological profile of rosacea in subjects who consulted in dermatological outpatient clinics in Brazil. MATERIALS & METHODS: A cross-sectional study was conducted in 13 dermatological outpatient clinics across the country. Patients with rosacea diagnosis were eligible for the study according to the investigator's clinical assessment. Clinical, social and demographic data were collected. The overall and regional rosacea prevalence was calculated, and association with baseline characteristics was analysed. RESULTS: A total of 3,184 subjects were enrolled, and rosacea prevalence was 12.7%. The southern region of Brazil presented a higher prevalence, followed by the southeast. The subjects in the rosacea group were older than those without rosacea (52.5 ±14.9 vs. 47.5 ±17.5; p<0.001). Moreover, the rosacea group was associated with Fitzpatrick's phototypes I and II, Caucasian ethnicity, a family history of rosacea, and facial erythema, however, no association with gender was found. The most prevalent clinical sign and clinical subtype in rosacea patients were erythema and erythematotelangiectatic, respectively. CONCLUSION: Rosacea is highly prevalent in Brazil, mostly in the southern region, associated with phototypes I and II and a family history.
Subject(s)
Dermatology , Rosacea , Humans , Brazil/epidemiology , Cross-Sectional Studies , Rosacea/epidemiology , Rosacea/complications , Erythema/complicationsABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) act as antipyretics, analgesics and anti-inflammatories. Among them, diclofenac and ibuprofen are the most consumed drugs worldwide. During the COVID-19 pandemic, some NSAIDs, such as dipyrone and paracetamol, have been used to alleviate the symptoms of the disease, causing an increase in the concentrations of these drugs in water. However, due to the low concentration of these compounds in drinking water and groundwater, few studies have been carried out on the subject, especially in Brazil. Thus, this study aimed to evaluate the contamination of the surface water, groundwater, and water treated with diclofenac, dipyrone, ibuprofen, and paracetamol at 3 cities (Orocó, Santa Maria da Boa Vista and Petrolândia) in the Brazilian semiarid region, in addition to analyzing the removal of these drugs by conventional water treatment (coagulation, flocculation, sedimentation, filtration and disinfection) in stations to each city. All drugs analyzed were detected in surface and treated waters. In groundwater, only dipyrone was not found. Dipyrone was seen in surface water with a maximum concentration of 1858.02 µg.L-1, followed by ibuprofen (785.28 µg.L-1), diclofenac (759.06 µg.L-1) and paracetamol (533.64 µg.L-1). The high concentrations derive from the increased consumption of these substances during the COVID-19 pandemic. During the conventional water treatment, the maximum removal of diclofenac, dipyrone, ibuprofen and paracetamol was 22.42%; 3.00%; 32.74%; and 1.58%, respectively, which confirms the inefficiency of this treatment in removing drugs. The variation in removal rate of the analyzed drugs is due to the difference in the hydrophobicity of the compounds.
ABSTRACT
Spinal cord injury (SCI) is an as yet untreatable neuropathology that causes severe dysfunction and disability. Cell-based therapies hold neuroregenerative and neuroprotective potential, but, although being studied in SCI patients for more than two decades, long-term efficacy and safety remain unproven, and which cell types result in higher neurological and functional recovery remains under debate. In a comprehensive scoping review of 142 reports and registries of SCI cell-based clinical trials, we addressed the current therapeutical trends and critically analysed the strengths and limitations of the studies. Schwann cells, olfactory ensheathing cells (OECs), macrophages and various types of stem cells have been tested, as well as combinations of these and other cells. A comparative analysis between the reported outcomes of each cell type was performed, according to gold-standard efficacy outcome measures like the ASIA impairment scale, motor and sensory scores. Most of the trials were in the early phases of clinical development (phase I/II), involved patients with complete chronic injuries of traumatic aetiology and did not display a randomized comparative control arm. Bone marrow stem cells and OECs were the most commonly tested cells, while open surgery and injection were the main methods of delivering cells into the spinal cord or submeningeal spaces. Transplantation of support cells, such as OECs and Schwann cells, resulted in the highest ASIA Impairment Scale (AIS) grade conversion rates (improvements in â¼40% of transplanted patients), which surpassed the spontaneous improvement rate expected for complete chronic SCI patients within 1 year post-injury (5-20%). Some stem cells, such as peripheral blood-isolated and neural stem cells, offer potential for improving patient recovery. Complementary treatments, particularly post-transplantation rehabilitation regimes, may contribute highly to neurological and functional recovery. However, unbiased comparisons between the tested therapies are difficult to draw, given the great heterogeneity of the design and outcome measures used in the SCI cell-based clinical trials and how these are reported. It is therefore crucial to standardize these trials when aiming for higher value clinical evidence-based conclusions.
Subject(s)
Nervous System Diseases , Spinal Cord Injuries , Humans , Cell- and Tissue-Based Therapy , Recovery of Function , Spinal Cord , Clinical Trials as TopicABSTRACT
In mice, oral Toxoplasma gondii infection induces severe ileitis. The aim of the present study was to investigate the impact of the P2X7 receptor (P2X7) on the inflammatory response to T. gondii-induced ileitis. Cysts of the ME49 strain of T. gondii were used to induce ileitis. The infected mice were euthanized on day 8 and ileal tissue and peripheral blood were collected for histopathological and immunohistochemical analyses. Ileal contractility, inflammatory mediators, inflammasome activation, quantitative PCR analysis of gene expression, and fecal microbiota were assessed using appropriate techniques, respectively. The infected P2X7-/- mice had greater disease severity, parasitic burden, liver damage, and intestinal contractility than the infected wild-type (WT) mice. Infection increased serum IL-6 and IFN-γ and tissue caspase-1 but not NLRP3 in P2X7-/- mice compared to WT mice. Bacteroidaceae, Rikenellaceae, and Rhodospirillales increased while Muribaculaceae and Lactobacillaceae decreased in the infected WT and P2X7-/- mice. Bacteroidia and Tannerellaceae increased in the P2X7-/- mice with ileitis. By contrast, Clostridiales and Mollicutes were absent in the P2X7-/- mice but increased in the WT mice. P2X7 protects mice against T. gondii infection by activating the inflammasome and regulating the local and systemic immune responses. Specific gut bacterial populations modulated by P2X7 determine disease severity.