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1.
J Neuroinflammation ; 21(1): 54, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383421

RESUMO

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by the aggregation of α-Synuclein (αSYN) building up intraneuronal inclusions termed Lewy pathology. Mounting evidence suggests that neuron-released αSYN aggregates could be central to microglial activation, which in turn mounts and orchestrates neuroinflammatory processes potentially harmful to neurons. Therefore, understanding the mechanisms that drive microglial cell activation, polarization and function in PD might have important therapeutic implications. Here, using primary microglia, we investigated the inflammatory potential of pure αSYN fibrils derived from PD patients. We further explored and characterized microglial cell responses to a chronic-type inflammatory stimulation combining PD patient-derived αSYN fibrils (FPD), Tumor necrosis factor-α (TNFα) and prostaglandin E2 (PGE2) (TPFPD). We showed that FPD hold stronger inflammatory potency than pure αSYN fibrils generated de novo. When combined with TNFα and PGE2, FPD polarizes microglia toward a particular functional phenotype departing from FPD-treated cells and featuring lower inflammatory cytokine and higher glutamate release. Whereas metabolomic studies showed that TPFPD-exposed microglia were closely related to classically activated M1 proinflammatory cells, notably with similar tricarboxylic acid cycle disruption, transcriptomic analysis revealed that TPFPD-activated microglia assume a unique molecular signature highlighting upregulation of genes involved in glutathione and iron metabolisms. In particular, TPFPD-specific upregulation of Slc7a11 (which encodes the cystine-glutamate antiporter xCT) was consistent with the increased glutamate response and cytotoxic activity of these cells toward midbrain dopaminergic neurons in vitro. Together, these data further extend the structure-pathological relationship of αSYN fibrillar polymorphs to their innate immune properties and demonstrate that PD-derived αSYN fibrils, TNFα and PGE2 act in concert to drive microglial cell activation toward a specific and highly neurotoxic chronic-type inflammatory phenotype characterized by robust glutamate release and iron retention.


Assuntos
Síndromes Neurotóxicas , Doença de Parkinson , Humanos , Doença de Parkinson/patologia , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Microglia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Sinais (Psicologia) , Inflamação/metabolismo , Neurônios Dopaminérgicos/patologia , Síndromes Neurotóxicas/metabolismo , Glutamatos/metabolismo , Ferro/metabolismo
2.
Odontology ; 112(2): 399-407, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37874511

RESUMO

To evaluate the osteogenic potential of platelet-rich fibrin (PRF) and low-level laser therapy (LLLT) on human stem cells from the apical papilla (SCAP) we isolated, characterized, and then cultured in an osteogenic medium cells with PRF and/or LLLT (660 nm, 6 J/m2-irradiation). Osteogenic differentiation was assessed by bone nodule formation and expression of bone morphogenetic proteins (BMP-2 and BMP-4), whereas the molecular mechanisms were achieved by qRT-PCR and RNA-seq analysis. Statistical analysis was performed by ANOVA and Tukey's post hoc tests (p < 0.05* and p < 0.01**). Although PRF and LLLT increased bone nodule formation after 7 days and peaked at 21 days, the combination of PRF + LLLT led to the uppermost nodule formation. This was supported by increased levels of BMP-2 and -4 osteogenic proteins (p < 0.005). Furthermore, the PRF + LLLT relative expression of specific genes involved in osteogenesis, such as osteocalcin, was 2.4- (p = 0.03) and 28.3- (p = 0.001) fold higher compared to the PRF and LLLT groups, and osteopontin was 22.9- and 1.23-fold higher, respectively (p < 0.05), after 7 days of interaction. The transcriptomic profile revealed that the combination of PRF + LLLT induces MSX1, TGFB1, and SMAD1 expression, after 21 days of osteogenic differentiation conditions exposition. More studies are required to understand the complete cellular and molecular mechanisms of PRF plus LLLT on stem cells. Overall, we demonstrated for the first time that the combination of PRF and LLLT would be an excellent therapeutic tool that can be employed for dental, oral, and craniofacial repair and other tissue engineering applications.


Assuntos
Osteogênese , Fibrina Rica em Plaquetas , Humanos , Fibrina Rica em Plaquetas/metabolismo , Proliferação de Células , Células Cultivadas , Células-Tronco , Diferenciação Celular , Lasers
3.
Eur Arch Psychiatry Clin Neurosci ; 273(6): 1359-1368, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36422680

RESUMO

Samples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not. We observed that older, male participants with higher education were more likely to donate a saliva sample. Self-reported bipolar disorder, ADHD, panic disorder, PTSD, substance use disorder, and social anxiety disorder were associated with lower odds of donating a saliva sample, whereas anorexia was associated with higher odds of donation. Male and younger participants showed higher odds of agreeing to record linkage. Participants with higher neuroticism scores and those with a history of bipolar disorder were also more likely to agree to record linkage whereas participants with a diagnosis of anorexia were less likely to agree. Increased likelihood of consent was associated with increased genetic susceptibility to anorexia and reduced genetic risk for depression, and schizophrenia. Overall, our results show moderate differences among these subsamples. Most current epidemiological studies do not search for attrition biases at the genetic level. The possibility to do so is a strength of samples such as the AGDS. Our results suggest that analyses can be made more robust by identifying attrition biases both on the phenotypic and genetic level, and either contextualising them as a potential limitation or performing sensitivity analyses adjusting for them.


Assuntos
Anorexia , Depressão , Humanos , Masculino , Depressão/epidemiologia , Depressão/genética , Austrália , Consentimento Livre e Esclarecido , DNA
4.
Twin Res Hum Genet ; 26(3): 209-214, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37476981

RESUMO

The recruitment of participants for research studies may be subject to bias. The Prospective Imaging Study of Ageing (PISA) aims to characterize the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). Participants approached to take part in PISA were selected from existing cohort studies with available genomewide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment, including the genetic predisposition to AD. We use a polygenic risk score (PRS) approach to test to what extent the genetic risk for AD, and related risk factors predict participation in PISA. We did not identify a significant association of genetic risk for AD with study participation, but we did identify significant associations with PRS for key causal risk factors for AD, IQ, household income and years of education. We also found that older and female participants were more likely to take part in the study. Our findings highlight the importance of considering bias in key risk factors for AD in the recruitment of individuals for cohort studies.


Assuntos
Doença de Alzheimer , Envelhecimento Cognitivo , Adulto , Humanos , Feminino , Doença de Alzheimer/genética , Predisposição Genética para Doença , Estudos Prospectivos , Austrália/epidemiologia , Fenótipo
5.
Clin Lab ; 67(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34758218

RESUMO

BACKGROUND: Platelet-rich fibrin (PRF) is a biomaterial widely used in the field of regenerative medicine. The purpose of this work was to analyze the structure and biomolecular characteristics of PRF through nine centrifugation parameters (CP) for its preparation, using a pool of blood samples of five volunteers. METHODS: The PRF obtained was analyzed by morphological and histological characteristics, as well as electronic and atomic force microscopy and growth factors determinations. RESULTS: A longer time of centrifugation showed taller clots and denser mesh fibrin in comparison with a short time (p < 0.05). The protocols with higher speed of centrifugation showed higher levels of PDGF-BB and VEGF. Higher levels of TGFß1 were found in protocols with a shorter centrifuge time. The mean platelet count (916.05 ± 23.73 cells x 103 cells x cm3) and its roughness (Ra) (616.5 ± 45.2 nm) did not show significant differences between different CP (p > 0.05). A significant correlation between fibrin density and levels of PDGF (r = 0.57) and VEGF (r = 0.52) was found. Additionally, the size of the clot had a significant correlation (r = -0.47) with TGFß1 levels. CONCLUSIONS: Different centrifugation parameters to obtain PRF have been reported. These results indicate that changes in the conditions to obtain PRF have a significant impact on their fibrin structure, cellular distribution, and biomolecular content, which can be decisive for its choice in the different clinical applications to be used. It is necessary to use a standardized centrifuge and protocol to guarantee high-quality PRF and clinical outcomes with less variability.


Assuntos
Fibrina Rica em Plaquetas , Plaquetas , Centrifugação , Fibrina , Humanos , Medicina Regenerativa
6.
J Clin Immunol ; 38(7): 794-803, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30264381

RESUMO

PURPOSE: CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida, but also by dermatophytes, Aspergillus, and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C. cassiicola. We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C. cassiicola and we searched for mutations in CARD9. METHODS: We reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting. RESULTS: The patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C. cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient. CONCLUSION: We describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C. cassiicola in a Colombian child.


Assuntos
Ascomicetos , Proteínas Adaptadoras de Sinalização CARD/genética , Predisposição Genética para Doença , Heterozigoto , Infecções Fúngicas Invasivas , Mutação , Feoifomicose/epidemiologia , Feoifomicose/etiologia , Fatores Etários , Idade de Início , Ascomicetos/genética , Ascomicetos/imunologia , Biomarcadores , Pré-Escolar , Colômbia/epidemiologia , Biologia Computacional/métodos , Análise Mutacional de DNA , Feminino , Humanos , Imuno-Histoquímica , Imunofenotipagem , Imageamento por Ressonância Magnética , Linhagem , Feoifomicose/diagnóstico , Feoifomicose/imunologia , Fenótipo , Tomografia Computadorizada por Raios X , Sequenciamento do Exoma
9.
Clin Lab ; 61(8): 973-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26427141

RESUMO

BACKGROUND: To develop a protocol for obtaining autologous platelet rich plasma in healthy individuals and to determine the concentration of five major growth factors before platelet activation. This protocol could be integrated into the guidelines of good clinical practice and research in regenerative medicine. METHODS: Platelet rich plasma was isolated by centrifugation from 38 healthy men and 42 women ranging from 18 to 59 years old. The platelet count and quantification of growth factors were analyzed in eighty samples, stratified for age and gender of the donor. Analyses were performed using parametric the t-test or Pearson's analysis for non-parametric distribution. P < 0.05 was considered statistically significant. RESULTS: Our centrifugation protocol allowed us to concentrate basal platelet counts from 1.6 to 4.9 times (mean = 2.8). There was no correlation between platelet concentration and the level of the following growth factors: VEGF-D (r = 0.009, p = 0.4105), VEGF-A (r = 0.0068, p = 0.953), PDGF subunit AA (p = 0.3618; r = 0.1047), PDGF-BB (p = 0.5936; r = 0.6095). In the same way, there was no correlation between donor gender and growth factor concentrations. Only TGF-ß concentration was correlated to platelet concentration (r = 0.3163, p = 0.0175). CONCLUSIONS: The procedure used allowed us to make preparations rich in platelets, low in leukocytes and red blood cells, and sterile. Our results showed biological variations in content of growth factors in PRP. The factors influencing these results should be further studied.


Assuntos
Doadores de Sangue , Protocolos Clínicos/normas , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Plasma Rico em Plaquetas , Medicina Regenerativa/normas , Adolescente , Adulto , Becaplermina , Centrifugação/normas , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Fator de Crescimento Derivado de Plaquetas/análise , Plasma Rico em Plaquetas/química , Plasma Rico em Plaquetas/citologia , Proteínas Proto-Oncogênicas c-sis/sangue , Controle de Qualidade , Padrões de Referência , Medicina Regenerativa/métodos , Fator de Crescimento Transformador beta/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Fator D de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
10.
Clin Lab ; 60(5): 869-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24839834

RESUMO

BACKGROUND: The main purpose of this study was to establish the prevalence of antibodies against five transfusion-transmissible infections (TTIs) in blood donors from one of the most important blood banks in Colombia. METHODS: A cross-sectional, descriptive and case control study was performed from a database of Higuera-Escalante blood bank, for a period of a year. Serum was used for donor screening. Surface antigens for hepatitis B (HbsAg), anti-hepatitis C antibodies, Chagas disease, syphilis, and HIV were identified. Chemiluminescent Microparticle Immunoassay (CMIA, Abbott Diagnostics) was performed. RESULTS: From 41,575 total donors analyzed, 1,226 were reactive for any of the infectious markers (total prevalence of 2.95%). The prevalence of specific infections was: Chagas disease 0.49%, HbsAg 0.21%, HCV 0.45%, HIV 0.12%, and syphilis 1.68%. Reactivity was more frequent in men (n = 785, 64%) with a mean age of 36.35 years. HIV was present in the youngest donors with a mean age of 26.5 years (IC 95%: 23.6 - 27.6); on the other hand, Chagas disease was found in the oldest donor population, with a mean age of 40 years (IC 95%: 39.1 - 41.3). CONCLUSIONS: Identifying the prevalence of circulating antibodies against transfusion transmissible infections allows us to establish an epidemiological profile of donors inhabiting the geographic catchment area of our blood bank. Total prevalence in this study was 2.95% for any of the five markers. Syphilis prevalence demonstrates its high distribution within the blood donor population of our country, although this result could be influenced by the high rate of false-reactive test. Chagas disease is endemic in Santander, Colombia, which correlates with the results obtained in this study.


Assuntos
Anticorpos/efeitos adversos , Anticorpos/sangue , Doadores de Sangue , Patógenos Transmitidos pelo Sangue , Transmissão de Doença Infecciosa , Reação Transfusional , Adulto , Anticorpos Antiprotozoários/sangue , Doadores de Sangue/estatística & dados numéricos , Doadores de Sangue/provisão & distribuição , Estudos de Casos e Controles , Colômbia/epidemiologia , Estudos Transversais , Transmissão de Doença Infecciosa/estatística & dados numéricos , Feminino , Anticorpos Anti-HIV/sangue , Anticorpos Anti-Hepatite/sangue , Humanos , Masculino , Treponema/imunologia , Treponema/patogenicidade , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/patogenicidade , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-39187305

RESUMO

Plants accumulate hundreds of thousands of specialized metabolites that participate in their interactions with the environment. Among these compounds, phenolics represent a large class, and they play important physiological roles, such as providing a first barrier against pathogens, cues to pollinators, and radiation protection. Maize is one of the most important crops worldwide for food, animal feed, and biofuels, and it has the potential to accumulate different phenolics in vegetative tissues as well as in seeds. Recent studies have identified a large number of phenolic compounds-with a diversity of chemical decorations-in different maize tissues, but these likely represent just a fraction of the metabolic diversity of maize. In this protocol, we describe a specific method for the extraction and quantification of maize phenolic compounds by ultra-high-pressure liquid chromatography-tandem multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS/MS) analysis. We provide detailed instructions for the extraction of phenolics using acidic methanol, and for the quantification of 33 different compounds in maize stems, including flavonoids, phenolic acids, and lignin precursors.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39187303

RESUMO

Anthocyanins are flavonoid pigments that accumulate in fruits and flowers that serve as attractants for pollinators and seed-dispersing organisms. Anthocyanins exhibit diverse chemical structures, characterized both by different anthocyanidin core structures and numerous chemical modifications of the anthocyanidin core. Here, we describe a protocol for the extraction and quantification of total anthocyanins, as well as for the characterization of anthocyanidin core structures and specific anthocyanins, using a spectrophotometer, high-performance liquid chromatography (HPLC), and ultra-high-performance liquid chromatography-two-dimensional mass spectrometry (UHPLC-MS/MS). The method involves anthocyanin extraction using acidic methanol, anthocyanin quantification using a spectrophotometer, determination of anthocyanidin core structure from hydrolyzed anthocyanin extracts using UHPLC-MS/MS, separation of different anthocyanins using HPLC, and characterization of specific anthocyanins using UHPLC-MS/MS. As an example, we describe how we have used this protocol to extract and quantify total anthocyanins from maize leaves, identify cyanidin as the core anthocyanidin structure, and characterize three specific anthocyanins that accumulate in maize leaves, each having a cyanidin core with decorations of a hexose group, and a malonyl or coumaroyl moiety.

13.
Diabetol Metab Syndr ; 16(1): 42, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360703

RESUMO

BACKGROUND: The burden of disease of diabetes in Colombia have increased in the last decades. Secondary prevention is crucial for diabetes control. Many patients already treated remain with poor glycemic control and without timely and appropriate treatment intensification. This has been called in the literature as Clinical Inertia. Updated information regarding clinical inertia based on the Colombian diabetes treatment guidelines is needed. OBJECTIVE: To measure the prevalence of clinical inertia in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients in healthcare institutions in Colombia, based on the recommendations of the current official guidelines. METHODS: An observational and retrospective cohort study based on databases of two Health Medical Organizations (HMOs) in Colombia (one from subsidized regimen and one from contributory regimen) was conducted. Descriptive analysis was performed to summarize demographic and clinical information. Chi-square tests were used to assess associations between variables of interest. RESULTS: A total of 616 patients with T2DM (308 for each regimen) were included. Median age was 61 years. Overall clinical inertia was 93.5% (87.0% in contributory regimen and 100% in subsidized regimen). Patients with Hb1Ac ≥ 8% in the subsidized regimen were more likely to receive monotherapy than patients in the contributory regimen (OR 2.33; 95% CI 1.41-3.86). CONCLUSIONS: In this study, the prevalence of overall clinical inertia was higher in the subsidized regime than in the contributory regime (100% vs 87%). Great efforts have been made to equalize the coverage between the two systems, but this finding is worrisome with respect to the difference in quality of the health care provided to these two populations. This information may help payers and clinicians to streamline strategies for reducing clinical inertia and improve patient outcomes.

14.
J Psychiatr Res ; 171: 346-353, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38354668

RESUMO

Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations. Participants (N = 1064; age range 12-17 years old; 58.8% female) were adolescents recruited for a general population survey on adolescent mental health in the Mexico City Metropolitan region and were genotyped. Childhood adversity exposure and externalizing disorders, specifically attention-deficit hyperactivity disorder (ADHD), conduct disorder, oppositional defiant disorder, and substance use disorder, were assessed via the computer-assisted World Mental Health Composite International Diagnostic Interview for adolescents. A greater externalizing PGS was associated with a greater odds of any externalizing disorder (OR = 1.29 [1.12, 1.48]; p < 0.01) and ADHD (OR = 1.40 [1.15, 1.70]; p < 0.01) in the whole sample, and in females in particular. There were no main effects of the externalizing PGS on conduct disorder, oppositional defiant disorder, or substance use disorder, nor did adversity exposure moderate these associations. Our results suggest that greater genetic propensity for externalizing disorders is associated with increased odds of any externalizing disorders and ADHD among Mexican adolescents, furthering our understanding of externalizing disorder manifestation in this population.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno da Conduta , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Feminino , Criança , Masculino , Estudo de Associação Genômica Ampla , México , Transtorno da Conduta/epidemiologia , Transtorno da Conduta/genética , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/complicações
15.
JTCVS Open ; 20: 174-182, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39296460

RESUMO

Objective: In patients with non-small cell lung cancer, lymph node assessment is essential for appropriate staging. The intrapulmonary lymph nodes (IPLNs) should be considered when assigning the N stage but are infrequently evaluated in Colombian centers, resulting in understaging that may hinder optimal treatment. Methods: We conducted a prospective study of IPLN dissection in patients with clinical stage I or II non-small cell lung cancer who underwent surgical resection at 9 institutions in Colombia between 2021 and 2023. IPLN dissection was performed by trained surgeons who collected lymph nodes from fresh specimens after resection and before formalin fixation. Results: One hundred patients were eligible for the analysis. Their mean age was 67 ± 10.9 years, and 76% were women. Most (74%) had adenocarcinoma, 20% had neuroendocrine tumors, and 6% had squamous cell carcinoma. Successful sampling and histopathologic analysis of at least one IPLN station was obtained in 85% of patients, 9% had upstaging due to positive N2 lymph nodes, and 5% had upstaging due to positive N1 lymph nodes. Among the patients with pN0 or pN1 disease, 3.2% (3 out of 91) were upstaged exclusively due to positive IPLNs. Conclusions: Fresh-specimen dissection to collect IPLNs is appropriate and feasible to achieve more accurate pathological staging in Colombian lung cancer patients. In clinical N0 patients, IPLN dissection maximizes selection for adjuvant therapy.

16.
Front Cell Infect Microbiol ; 12: 883759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694548

RESUMO

The persistence of erythrocytes infected with Plasmodium falciparum gametocytes in the bloodstream is closely related to the modulation of their mechanical properties. New drugs that increase the stiffness of infected erythrocytes may thus represent a novel approach to block malaria parasite transmission. The phosphodiesterase inhibitor tadalafil has been shown to impair the ability of infected erythrocytes to circulate in an in vitro model for splenic retention. Here, we used a humanized mouse model to address in vivo the effect of tadalafil on the circulation kinetics of mature gametocyte-infected erythrocytes. We show that stiff immature gametocyte-infected erythrocytes are retained in the spleen of humanized mice at rates comparable to that of the in vitro model. Accordingly, tadalafil-induced stiffening of mature gametocyte-infected erythrocytes impairs their circulation in the bloodstream and triggers their retention by the spleen. These in vivo results validate that tadalafil is a novel drug lead potentially capable of blocking malaria parasite transmission by targeting GIE mechanical properties.


Assuntos
Malária Falciparum , Plasmodium falciparum , Animais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Camundongos , Inibidores de Fosfodiesterase , Baço , Tadalafila/farmacologia
17.
Ann Med Surg (Lond) ; 75: 103380, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35242326

RESUMO

End-of-life care is an increasingly relevant topic due to advances in biomedical research and the establishment of new disciplines in evidence-based medicine and bioethics. Euthanasia and assisted suicide are two terms widely discussed in medicine, which cause displeasure on many occasions and cause relief on others. The evolution of these terms and the events associated with their study have allowed the evaluation of cases that have established useful definitions for the legal regulation of palliative care and public policies in the different health systems. However, there are still many aspects to be elucidated and defined. Based on the above, this review aimed to compile relevant historical aspects on the evolution of euthanasia and assisted suicide, which will allow understanding the use and research of these terms.

18.
J Prim Care Community Health ; 13: 21501319221121462, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36112863

RESUMO

INTRODUCTION: Assisted suicide and euthanasia are controversial issues today and have been throughout the history of humanity, mainly because there are individuals for and against them. Currently, the legalization of these practices is being discussed in Chile, and the perception of physicians regarding this issue is unknown. Therefore, this study aimed to assess physicians' perception of Chile's euthanasia and assisted suicide. METHODS: A nationwide cross-sectional study was carried out in Chile. A questionnaire of physicians' attitudes and opinions on assisted suicide and euthanasia was used. The population was the doctors who work in Chile, and the sample was convenient with a sample calculation of 384 physicians. About 20 variables were considered and included in a form created through the Google forms option, which was distributed through social networks: LinkedIn, Facebook, Twitter, and WhatsApp. To guarantee the anonymity of the participants, the option to request and remember the participant's email was deactivated. A generated database allowed the quantitative analysis of the variables and their expression through frequencies, percentages, and graphs. The European University of the Atlantic's research ethics committee approved this study as stated in the document CE-55 of March 2021. RESULTS: A total of 410 physicians were surveyed. 50.7% (n = 208) of the participants identified themselves as men, and 69.8% (n = 286) were Chilean. The city of Santiago was the area of residence of 72.9% (n = 299) of the participants. About 34.6% (n = 142) of participants were general practitioners, and 39.3% (n = 161) of the physicians had more than 20 years of experience. About 68.7% had favorable attitudes toward euthanasia and 54.4% toward assisted suicide; However, although the majority favored legalizing euthanasia and assisted suicide, approximately 48.8% stated that they would not participate in an assisted suicide procedure. CONCLUSIONS: There was evidence of support for the implementation and legalization of euthanasia and assisted suicide by physicians in Chile. However, there are still professionals who have not yet decided on a definitive position on these practices.


Assuntos
Eutanásia , Médicos , Suicídio Assistido , Atitude do Pessoal de Saúde , Chile , Estudos Transversais , Humanos , Masculino , Percepção
19.
Burns ; 48(4): 995-1003, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34696951

RESUMO

INTRODUCTION: A burn injury is a very painful experience, with subsequent emotional problems, which have been gaining relevance to the extent that survival from burns has improved. Among the alterations of the mental sphere in this population is Acute Stress Disorder (ASD) that has been described in up to one-third of patients with major burns. METHODOLOGY: A nested case-control study was carried out in a cohort of hospitalized patients in a burn referral unit, in patients over 16 years of age. A total of 135 patients, 41 cases, and 94 controls were included. All of them underwent a psychiatric interview, a standardized form was filled out on sociodemographic and clinical information, and the PID-5-BF scale was applied to evaluate associated personality elements. The diagnosis of acute stress was made with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. RESULTS: The incidence of acute stress was 23.4%. When the clinical and sociodemographic characteristics of both the cases and the controls were compared, the risk factors were subsidized insurance, flame burn, burn in a special area, third-degree burn, high pain, stay in the Intensive Care Unit (ICU), peritraumatic amnesia and life threat. Patients also had a higher percentage of burned body surface, higher average pulse, longer hospital length of stay, higher average in the negative affect variable and in the psychoticism variable of the PID-5-BF scale. But for the multivariate analysis using logistic regression, the model that best explains the presence of acute stress only includes the variables life threat (Odds Ratio adjusted (ORa): 117.0; Confidence Interval (CI): 10.9-1258.5), severe pain (ORa: 9.9; CI: 1.8-52.8), electrical burn (ORa: 20.8; CI: 17.2-250), burn in a special area (ORa: 8.9; CI: 1, 0-76.8), third-degree burn (ORa: 10.4; CI: 0.7-166.7). CONCLUSION: Acute stress disorder is frequent in the hospitalised burn population, and is more frequent than in other types of trauma. Associated factors with the presentation of Acute Stress Disorder are the feeling of life threat at the time of the burn, having pain classified as strong (Visual Analog Scale (VAS) 5-10), electrical burn, and burns in special areas.


Assuntos
Queimaduras por Corrente Elétrica , Queimaduras , Transtornos de Estresse Traumático Agudo , Queimaduras/complicações , Queimaduras/epidemiologia , Queimaduras por Corrente Elétrica/complicações , Estudos de Casos e Controles , Humanos , Tempo de Internação , Dor/complicações , Estudos Retrospectivos , Transtornos de Estresse Traumático Agudo/epidemiologia
20.
Int Med Case Rep J ; 14: 649-656, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588822

RESUMO

Pressure injury (PI) corresponds to a skin damage of ischemic aetiology that affects the integrity of the skin and is produced by prolonged pressure or friction between a hard internal and external surface. Treatment can be challenging when there is no resolution with usual care. The use of autologous platelet-rich plasma (APRP) gel arises as a therapeutic possibility in the presence of chronic pressure injuries. The case of a patient with chronic PI who has been treated with APRP is presented, achieving resolution of the lesion.

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