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1.
Cancer ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896056

RESUMEN

BACKGROUND: There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications. METHODS: The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021. RESULTS: Screening rates increased for all tests across different time periods (2000-2007, 2008-2016, and 2017-2021) and was the most influential factor for NPM1, FLT3-ITD, and next-generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p < .001), whereas FLT3-ITD testing increased from 38.1% to 74.1% and 95.9% (p < .0001). NGS testing was not performed between 2000-2007 and only reached 3.5% in 2008-2016, but significantly increased to 72% in 2017-2021 (p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702-7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901-2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy. CONCLUSIONS: This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real-world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades.

2.
J Pediatr Psychol ; 49(4): 266-278, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38070171

RESUMEN

OBJECTIVE: Internet-based interventions may positively impact maternal symptoms of postnatal depression and anxiety. This study assessed the feasibility, acceptability, perceived usefulness, and preliminary effectiveness of an m-Health version of "What Were We Thinking?" (m-WWWT). METHODS: A mixed-methods with a 2-arm randomized parallel design was used. From a total of 477 women, 157 met the inclusion criteria. 128 first-time mothers of full-term infants, aged 4-10 weeks, who received health care at primary public health centers in Chile, were randomly assigned to the experimental (EG, n = 65) or control (CG, n = 63) groups; data of 104 of them (53 and 51, respectively) was analyzed. We used percentages and rates to measure feasibility outcomes and mixed analysis of variance (ANOVA) and latent class analyses (LCA) to assess preliminary effectiveness. Participants completed questionnaires on mental health, social support, and maternal self-efficacy upon recruitment and 3 months after completing the intervention. For the qualitative component, 12 women from the EG were interviewed. RESULTS: Quantitative results show good feasibility outcomes, such as high recruitment (82%), low attrition (EG = 12% and CG = 17%), and high follow-up (EG = 97% and CG = 91%) rates. Qualitative results indicate high acceptability and perceived usefulness of m-WWWT. Mixed ANOVA did not show significant differences between the groups (all p >.05). However, multinomial regression analysis in LCA showed that women with low baseline symptoms of depression and anxiety benefit from the intervention (B = 0.43, 95% confidence interval 1.09-2.16). CONCLUSION: m-WWWT is feasible to be implemented in Chile; future studies are needed to assess the intervention's effectiveness.


Asunto(s)
Depresión Posparto , Intervención basada en la Internet , Humanos , Femenino , Depresión Posparto/terapia , Depresión Posparto/psicología , Depresión/psicología , Chile , Estudios de Factibilidad , Ansiedad/psicología
3.
Molecules ; 29(12)2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38930804

RESUMEN

Our hypothesis that controlled ozone applications interfere with the redox balance of a biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication) has been verified over the past two decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes and type 2 diabetes, and in the prevention of intoxications. Low-dose ozone acts as a redox bioregulator: the restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase in the antioxidant repair markers, here mainly shown as a glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, and relevant data are displayed, evaluated and comprehensively discussed: the repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone-treated groups and depending on the indication, the stress markers are simultaneously reduced, and the redox system regains its balance.


Asunto(s)
Mitocondrias , Oxidación-Reducción , Estrés Oxidativo , Ozono , Especies Reactivas de Oxígeno , Estrés Oxidativo/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Antioxidantes/farmacología , Biomarcadores
4.
Xenotransplantation ; 30(5): e12823, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37695105

RESUMEN

BACKGROUND: The shortage of available transplant organs has made it necessary to search for alternatives, one of which is xenotransplantation. However, the use of animal organs could face rejection from society and the personnel involved in its implementation. OBJECTIVES: (a) to analyze the attitudes of Veterinary Degree students in six Spanish Universities towards xenotransplantation; and (b) to determine the factors that affect its acceptance. METHODS: Of the 2815 students surveyed in the degree program, 2683 valid surveys were obtained. Attitudes towards organ xenotransplantation were evaluated using a validated questionnaire of organ donation. RESULTS: If xenotransplantation was confirmed as a clinical reality, 93% (n = 2493) of those surveyed would accept a xenotransplanted organ, whilst 7% would not. If the results of xenotransplantation were worse than those obtained with human donors and it entailed more risk, 12% (n = 318) would be in favor. 56% (n = 1497) of the students would accept a xenotransplantation provisionally pending the arrival of a human organ. Attitudes towards xenotransplantation were affected by the academic year in which a student was studying, with more favorable attitudes among students in the last year (88% in first year vs. 95% in fifth year; p < .001). More favorable attitudes are also observed depending on the attitude they have towards organ transplantation, with those students being more in favor of donating their organs when they die (94% vs. 88%; p < .001). CONCLUSION: Veterinary students would have a very favorable attitude toward xenotransplantation if these animal organs functioned as well as human organs. Therefore, these students could play an important role in the future promotion of this technique.


Asunto(s)
Trasplante de Órganos , Obtención de Tejidos y Órganos , Animales , Humanos , Trasplante Heterólogo , España , Actitud , Estudiantes , Encuestas y Cuestionarios
5.
Int J Mol Sci ; 24(21)2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37958730

RESUMEN

The best form of prevention against human infection through bacteria, viruses, and other parasites is ozone disinfection of wastewater and drinking water as a highly effective, well-known method. Various preclinical studies showed promising results, which are being revisited and reconsidered in times of pandemics and led to interesting results in recent clinical trials and reports, as presented by the example of protective measures against COVID-19 in particularly vulnerable clinical personnel. The application of ozone in the form of the low-dose concept induces its regulation by interference of ozone or its peroxides into the redox equilibrium of the biological system, which finally results in the restoration of the glutathione equilibrium. The antioxidant system is activated, the immune system is modulated, and thus the defense mechanisms are improved. In patients with rheumatoid arthritis, repeated ozone treatments have led to new findings in "immunomodulation" through ozone. The more effective immune response is discussed as the response of innate immune memory and opens interesting aspects for complementary treatment of autoimmune diseases.


Asunto(s)
Agua Potable , Ozono , Humanos , Ozono/farmacología , Desinfección/métodos , Aguas Residuales , Oxidación-Reducción
6.
Psychother Res ; 33(5): 625-639, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36404291

RESUMEN

OBJECTIVE: : The aim of the study was to characterize the subjective experience of recovery from depression based on the perspective of those who suffer from it. METHOD: : Forty participants from two South American countries, who had been or were currently being treated for depression, took part in semi-structured and in-depth interviews. Most participants were female (78%), with ages ranging from 22 to 63 years. Interviews were analyzed using Grounded Theory, creating a hierarchy of categories that represent participants' experience of recovery. The categories were subsequently organized around an emergent central phenomenon. RESULTS: : "Transformation of the experience of the depressed self" was constructed as the main phenomenon that accounts for the subjective understanding of recovery. This transformation consists in an increase in self-acceptance, self-appreciation, and auto-biographical contextualization, coupled with an increase in agency and empowerment. CONCLUSION: : Recovery is experienced as a multidimensional process that goes beyond the absence of symptoms. Change is experienced as a result of active self-management and commitment. The relevance of person-centered perspectives and their subjectivity for managing depression is discussed.


Asunto(s)
Depresión , Pacientes , Humanos , Femenino , Masculino , Depresión/terapia , Investigación Cualitativa , Teoría Fundamentada
7.
Antimicrob Agents Chemother ; 66(1): e0142521, 2022 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-34694879

RESUMEN

Failure of treatment of cutaneous leishmaniasis with antimonial drugs and miltefosine is frequent. Use of oral combination therapy represents an attractive strategy to increase efficacy of treatment and reduce the risk of drug resistance. We evaluated the potency of posaconazole, itraconazole, voriconazole, and fluconazole and the potential synergy of those demonstrating the highest potency, in combination with miltefosine (HePC), against infection with Leishmania (Viannia) panamensis. Synergistic activity was determined by isobolograms and calculation of the fractional inhibitory concentration index (FICI), based on parasite quantification using an ex vivo model of human peripheral blood mononuclear cells (PBMCs) infected with a luciferase-transfected, antimony and miltefosine sensitive line of L. panamensis. The drug combination and concentrations that displayed synergy were then evaluated for antileishmanial effect in 10 clinical strains of L. panamensis by reverse transcription-quantitative (qRT-PCR) of Leishmania 7SLRNA. High potency was substantiated for posaconazole and itraconazole against sensitive as well as HePC- and antimony-resistant lines of L. panamensis, whereas fluconazole and voriconazole displayed low potency. HePC combined with posaconazole (Poz) demonstrated evidence of synergy at free drug concentrations achieved in plasma during treatment (2 µM HePC plus 4 µM Poz). FICI, based on 70% and 90% reduction of infection, was 0.5 for the sensitive line. The combination of 2 µM HePC plus 4 µM Poz effected a significantly greater reduction of infection by clinical strains of L. panamensis than individual drugs. Orally administrable miltefosine/posaconazole combinations demonstrated synergistic antileishmanial capacity ex vivo against L. panamensis, supporting their potential as a novel therapeutic strategy to improve efficacy and effectiveness of treatment.


Asunto(s)
Antiprotozoarios , Leishmania guyanensis , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Azoles/farmacología , Humanos , Leucocitos Mononucleares , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapéutico
8.
Int J Mol Sci ; 22(15)2021 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-34360655

RESUMEN

Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.


Asunto(s)
Antioxidantes/administración & dosificación , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Estrés Oxidativo , Ozono/administración & dosificación , Animales , Artritis Experimental/etiología , Artritis Experimental/patología , Artritis Reumatoide/etiología , Artritis Reumatoide/patología , Catalasa/metabolismo , Citocinas/metabolismo , Glutatión/metabolismo , Humanos , Inflamación/etiología , Inflamación/patología , Oxidantes Fotoquímicos/administración & dosificación , Oxidación-Reducción , Ratas
9.
Infect Immun ; 88(3)2020 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-31818959

RESUMEN

The immune mechanisms that contribute to the efficacy of treatment of cutaneous leishmaniasis (CL) are not fully understood. The aim of this study was to define immune correlates of the outcome of treatment of CL caused by Leishmania (Viannia) species during standard of care treatment with pentavalent antimonials. We conducted a comparative expression profiling of immune response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from CL patients before and at the end of treatment (EoT) with meglumine antimoniate. The ex vivo response of PBMCs to L (V) panamensis partially reflected that of lesion microenvironments. Significant downregulation of gene expression profiles consistent with local innate immune responses (monocyte and neutrophil activation and chemoattractant molecules) was observed at EoT in biopsy specimens of patients who cured (n = 8), compared to those from patients with treatment failure (n = 8). Among differentially expressed genes, pretreatment expression of CCL2 was significantly predictive of the therapeutic response (receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.82, P = 0.02). Polymorphisms in regulatory regions of the CCL2 promoter were analyzed in a pilot cohort of DNA samples from CL patients (cures, n = 20, and treatment failure, n = 20), showing putative association of polymorphisms rs13900(C/T) and rs2857656(G/C) with treatment outcome. Our data indicate that dampening gene expression profiles of monocyte and neutrophil activation characterize clinical cure after treatment of CL, supporting participation of parasite-sustained inflammation or deregulated innate immune responses in treatment failure.


Asunto(s)
Antiprotozoarios/uso terapéutico , Citocinas/metabolismo , Inmunidad Innata/fisiología , Leishmania/inmunología , Leishmaniasis/tratamiento farmacológico , Leishmaniasis/inmunología , Antimoniato de Meglumina/uso terapéutico , Perfilación de la Expresión Génica , Humanos , Leishmaniasis/metabolismo , Leucocitos Mononucleares/metabolismo , Proteínas Quimioatrayentes de Monocitos/metabolismo , Monocitos/metabolismo
10.
Infect Immun ; 85(3)2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28052994

RESUMEN

Infection by Leishmania (Viannia) panamensis, the predominant etiologic agent for cutaneous leishmaniasis in Colombia, is characterized by a chronic mixed inflammatory response. Current treatment options are plagued by toxicity, lengthy treatment regimens, and growing evidence of drug resistance. Immunotherapy, modulating the immune system to mount a protective response, may provide an alternate therapeutic approach. We investigated the ability of the Toll-like receptor 9 (TLR9) ligand CpG to modulate established disease in the L (V) panamensis mouse model. Treatment of established infection with a high dose (50 µg) of CpG ameliorated disease and lowered parasite burden. Interestingly, immediately after treatment there was a significant increase in transforming growth factor ß (TGF-ß) and concomitantly an increase in T regulatory cell (Treg) function. Although a general reduction in cell-mediated immune cytokine and chemokine (gamma interferon [IFN-γ], interleukin 10 [IL-10], IL-13, IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-4, and MIP-1α) responses of the treated mice was observed, certain chemokines (RANTES, monocyte chemoattractant protein 1[MCP-1], and IP-10) were increased. Further, in peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis, CpG treatment similarly exhibited a dose-response effect on the production of IFN-γ, IL-17, IL-10, and IL-13, with reductions observed at higher doses. To further understand the underlying mechanisms and cell populations driving the CpG mediated response, we examined the ex vivo dose effects mediated by the TLR9+ cell populations (dendritic cells, macrophages, and B cells) found to accumulate labeled CpG in vivo Notably, B cells altered the production of IL-17, IL-13, and IFN-γ, supporting a role for B cells functioning as antigen-presenting cells (APCs) and/or regulatory cells during infection. Interestingly, B cells have been previously demonstrated as a primary type of APC in patients infected with L (V) panamensis and thus may be useful targets of immunotherapy. Collectively, our results show that CpG-induced immune regulation leads to a dampening of the host immune response and healing in the mouse model, and it may provide an alternate approach to treatment of cutaneous leishmaniasis caused by L (V) panamensis.


Asunto(s)
Leishmania guyanensis/inmunología , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Mucocutánea/metabolismo , Oligodesoxirribonucleótidos/metabolismo , Receptor Toll-Like 9/metabolismo , Adulto , Animales , Enfermedad Crónica , Citocinas/metabolismo , Femenino , Humanos , Inmunomodulación , Leishmaniasis Mucocutánea/parasitología , Leishmaniasis Mucocutánea/patología , Ligandos , Masculino , Ratones , Persona de Mediana Edad , Carga de Parásitos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Adulto Joven
11.
Antimicrob Agents Chemother ; 58(1): 144-52, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24145529

RESUMEN

Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by Leishmania (Viannia) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six Leishmania (Viannia) braziliensis and six Leishmania (Viannia) panamensis strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults ≥55 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the Leishmania drug transporter genes abca2, abca3, abcc2, abcc3, abcg4, abcg6, and LbMT was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC50], 10.7 µmol/liter) were more susceptible to miltefosine than promastigotes (median EC50, 55.3 µmol/liter) (P < 0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC50 of >32 µmol/liter (the upper limit of intracellular amastigote assay), occurred in L. panamensis infection in a child and in L. braziliensis infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT/ß-tubulin, 0.42- to 0.26-fold [P = 0.039] and 0.70- to 0.57-fold [P = 0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype. Leishmania ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (r = -0.605; P = 0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal leishmaniasis.


Asunto(s)
Leishmania/efectos de los fármacos , Leishmania/patogenicidad , Leishmaniasis Cutánea/tratamiento farmacológico , Fosforilcolina/análogos & derivados , Transportador de Casetes de Unión a ATP, Subfamilia G , Transportadoras de Casetes de Unión a ATP/metabolismo , Adolescente , Adulto , Niño , Resistencia a Medicamentos , Femenino , Humanos , Leishmaniasis Cutánea/metabolismo , Masculino , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Fosforilcolina/uso terapéutico , Estudios Prospectivos , Insuficiencia del Tratamiento , Adulto Joven
12.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38543177

RESUMEN

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common arthritic diseases. Medical ozone has demonstrated its effectiveness in combination therapy with methotrexate or non-steroidal anti-inflammatory drugs for RA and OA, respectively. Although RA and OA have been compared from different points of view, few studies have considered their redox status in spite of the oxidative processes that are involved in both diseases. The aim of this study was to compare RA with OA, evaluating their redox status and the effects of ozone on their clinical response to combined therapy with ozone. The redox status of 80 patients was determined: antioxidant defenses, injury markers, two subjective variables (pain and disability), and levels of antibodies against cyclic citrullinated peptides were evaluated. Oxidative stress and clinical response to combined therapy with ozone was higher than in the case of RA. After medical ozone treatment, there was an increase in antioxidant defense and a decrease in injury markers as well as pain, disability, and autoantibody concentrations. Redox biomarkers were able to differentiate between both arthritic diseases and combined therapy with ozone (methotrexate + ozone), showing a therapeutic selectivity for RA in comparison with OA.

13.
iScience ; 27(5): 109773, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38711445

RESUMEN

Drug resistance threatens the effective control of infections, including parasitic diseases such as leishmaniases. Neutrophils are essential players in antimicrobial control, but their role in drug-resistant infections is poorly understood. Here, we evaluated human neutrophil response to clinical parasite strains having distinct natural drug susceptibility. We found that Leishmania antimony drug resistance significantly altered the expression of neutrophil genes, some of them transcribed by specific neutrophil subsets. Infection with drug-resistant parasites increased the expression of detoxification pathways and reduced the production of cytokines. Among these, the chemokine CCL3 was predominantly impacted, which resulted in an impaired ability of neutrophils to attract myeloid cells. Moreover, decreased myeloid recruitment when CCL3 levels are reduced was confirmed by blocking CCL3 in a mouse model. Collectively, these findings reveal that the interplay between naturally drug-resistant parasites and neutrophils modulates the infected skin immune microenvironment, revealing a key role of neutrophils in drug resistance.

14.
PLoS Negl Trop Dis ; 18(5): e0012156, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38709850

RESUMEN

The multifactorial basis of therapeutic response can obscure the relation between antimicrobial drug susceptibility and clinical outcome. To discern the relationship between parasite susceptibility to meglumine antimoniate (SbV) and therapeutic outcome of cutaneous leishmaniasis, risk factors for treatment failure were considered in evaluating this relationship in ninety-one cutaneous leishmaniasis patients and corresponding clinical strains of Leishmania (Viannia) panamensis. Parasite susceptibility to 32 µg SbV/mL (plasma Cmax) was evaluated in primary human macrophages, PBMCs, and U937 macrophages. Early parasitological response to treatment was determined in lesions of a subgroup of patients, and pathogenicity of Sb-resistant and sensitive clinical strains was compared in BALB/c mice. Parasite survival in cell models and patient lesions was determined by qRT-PCR of Leishmania 7SLRNA transcript. Parasite loads in BALB/c mice were quantified by limiting dilution analysis. The disparate Sb-susceptibility of parasite subpopulations distinguished by isoenzyme profiles (zymodemes) was manifest in all cell models. Notably, Sb-resistance defined by parasite survival, was most effectively discerned in U937 macrophages compared with primary human host cells, significantly higher among strains from patients who failed treatment than cured and, significantly associated with treatment failure. Each unit increase in transformed survival rate corresponded to a 10.6-fold rise in the odds of treatment failure. Furthermore, treatment failure was significantly associated with naturally Sb-resistant zymodeme 2.3 strains, which also produced larger lesions and parasite burdens in BALB/c mice than Sb-sensitive zymodeme 2.2 strains. The confounding effect of host risk factors for treatment failure in discerning this association was evidenced in comparing strains from patients with and without the defined risk factors for treatment failure. These results establish the association of natural resistance to meglumine antimoniate with treatment failure, the importance of host risk factors in evaluating drug susceptibility and treatment outcome, and the clinical and epidemiological relevance of natural Sb-resistance in L. (V.) panamensis subpopulations.


Asunto(s)
Antiprotozoarios , Resistencia a Medicamentos , Leishmaniasis Cutánea , Macrófagos , Antimoniato de Meglumina , Meglumina , Ratones Endogámicos BALB C , Compuestos Organometálicos , Insuficiencia del Tratamiento , Animales , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , Antimoniato de Meglumina/uso terapéutico , Antimoniato de Meglumina/farmacología , Humanos , Antiprotozoarios/uso terapéutico , Antiprotozoarios/farmacología , Femenino , Meglumina/uso terapéutico , Meglumina/farmacología , Compuestos Organometálicos/uso terapéutico , Compuestos Organometálicos/farmacología , Ratones , Macrófagos/parasitología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Leishmania guyanensis/efectos de los fármacos , Adulto , Persona de Mediana Edad , Adulto Joven , Carga de Parásitos , Adolescente
15.
Front Med (Lausanne) ; 11: 1380129, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38751980

RESUMEN

Objective: Arboviruses pose a challenge in ensuring the supply of pathogen-free blood components because they are not routinely screened in blood banks, and blood components from infected asymptomatic donors could be transfused. This study aimed to detect and characterize arboviral infections in Colombian blood donors. Methods: In a cross-sectional study, the prevalence of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses and co-infections of blood donors were compared between an epidemic period (November 2019-February 2020, n = 462) and an endemic period (November 2021-August 2022, n = 1,119). Viral RNA from each donor serum was purified, and the viruses were detected using a previously standardized multiplex hemi-nested RT-PCR protocol. Subsequently, donors who tested positive were surveyed 15 days after the detection of the virus to identify clinical characteristics related to the arboviral infection. The prevalences of each virus were presented as percentages and compared between epidemic and endemic periods. Results: Significantly higher prevalences were found in the epidemic period compared with the endemic period for DENV (14.5 vs. 1.9%), ZIKV (7.8 vs. 0.3%), CHIKV (8 vs. 3.3%), and co-infections (4.3 vs. 0.2%). The survey response rate of positive donors in the two periods was 83/175 (47%). In total, 57% of the donors surveyed were asymptomatic. Symptomatic donors most frequently reported headache (31%), malaise (13%), arthralgia (10%), and fever/chills (8%). Conclusion: The prevalence observed in epidemic and endemic periods was higher than that reported in other studies in the Americas. The high proportion of asymptomatic cases found, in addition to the mild and nonspecific manifestations among the symptomatic, may limit the effectiveness of the donor selection criteria used to mitigate the risk of transfusion-transmitted arboviruses.

16.
Am J Trop Med Hyg ; 108(3): 555-560, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36716739

RESUMEN

The endosymbiotic Leishmania RNA virus 1 (LRV1) has been associated with severity and clinical manifestations of American tegumentary leishmaniasis caused by species of the Leishmania (Viannia) subgenus. Between and within Leishmania species, and among endemic countries, the prevalence of LRV is highly variable. The LRV virus has not been detected in L. (V.) panamensis, the second-most prevalent species in Central America and Colombia. However, no systematic screening of LRV has been conducted in L. (V.) panamensis, and thus it is still controversial whether this virus is truly absent from the species. We sought to determine the prevalence of LRV1 in L. (V.) panamensis clinical strains isolated from patients with cutaneous leishmaniasis (CL), from different geographic areas of Colombia. We analyzed 219 clinical strains; 78% were L. (V.) panamensis, 18% were L. (V.) braziliensis, and 4% were L. (V.) guyanensis. Screening for LRV1 was performed by quantitative reverse transcription-polymerase chain reaction. The LRV1 was detected in 18% (7 of 40) of L. (V) braziliensis strains, and was not detected in any of the L. (V.) guyanensis or L. (V.) panamensis strains. The LRV1-positive L. (V). braziliensis strains came from the Amazon Basin. Of the seven LRV1-positive strains, two were isolated from patients with mucocutaneous leishmaniasis, and the remaining from patients with CL. Our results confirm the absence of LRV1 in L. (V.) panamensis in Colombia.


Asunto(s)
Leishmania braziliensis , Leishmania , Leishmaniasis Cutánea , Leishmaniasis Mucocutánea , Virus ARN , Humanos , Colombia , Leishmaniasis Mucocutánea/epidemiología
17.
Digit Health ; 9: 20552076231203920, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37786403

RESUMEN

Introduction: There is sufficient evidence about the effectiveness of internet-based interventions; however, the users' level of adoption and utilization remains low, with this phenomenon requiring adequate explanation. Objective: The aim of this qualitative study was to explore the users' perceptions and experience of a web-based program (ASCENSO), designed to complement (usual) in-person depression treatment. Method: Twelve participants of the ASCENSO program, comprised of adult individuals (M = 44.3, SD = 13.4) of both genders (67% women) undergoing treatment for depression, were interviewed through semi-structured interviews. The data obtained from these interviews were analyzed utilizing a constructivist grounded theory approach. The interviews were transcribed and analyzed by trained coders. A constant comparative analysis of emergent themes was conducted. Results: These show that users employ and appreciate the program when their interaction with it emulates a "humanized relationship," that is, when the program is proactive in assisting users with their requests and when it responds in a pertinent and individualized manner to their emotional states and needs. Conclusions: Our findings highlight the challenges associated with the development of algorithms capable of attracting different potential users. These should be designed to generate a virtual relationship that emulates human interaction and targets the characteristics of each user, for example, considering the specific phenomenology of their health condition, their present emotional states, and perceived needs. Elements that will vary as mental symptomatology evolve.

18.
Rev Esp Salud Publica ; 972023 Jan 27.
Artículo en Español | MEDLINE | ID: mdl-36705053

RESUMEN

OBJECTIVE: The term trans brings together all transgender identities. The early social transition towards the affirmed gender has benefits in the child's development. For families, transit is a period of great uncertainty, requiring support aimed at families of trans minors. The aim of this paper was to explore the needs and experiencies of parents and close-relatives who supported the social transition of their children. METHODS: We worked with focus groups of functional families of transgender minors who had begun the transition (n=14), with a medium-high educational level and who belonged to urban areas of Tenerife. Through a semi-structured interview, they commented on their experiences in the process of supporting the social transition of their children. The data was recorded in a video recording and processed through content analysis and categorization. RESULTS: Early social transition had positive and immediate benefits on child development as well as in the reduction of anxiety. There was a general improvement in mood, self-esteem, and social and family relationships. The accompaniment of specialists and associations helped in the different social situations and favoured resilience. CONCLUSIONS: Early social transition is positive in the personal and socio-family sphere of the minor. To improve their resilience, families demand accompaniment in this process, as well as meeting other trans people who serve as transpositive references. In addition, they point out the need for specific training in health professionals.


OBJETIVO: El término trans aglutina a todas las identidades transgénero. La transición social temprana hacia el género sentido tiene beneficios en el desarrollo del menor. Para las familias, el tránsito es un periodo de grandes incertidumbres, siendo necesario el acompañamiento dirigido a las familias de menores trans. El objetivo del artículo fue explorar, desde una perspectiva paterna y familiar, las necesidades y experiencias sobre el tránsito de menores trans que sirvieran de referente a otros padres/madres que apoyan el tránsito social de sus hijos e hijas. METODOS: Se trabajó con grupos focales de familias funcionales de menores transgénero que habían iniciado la transición (n=14), de nivel educativo medio-alto y que pertenecían a zonas urbanas de Tenerife. Mediante entrevista semiestructurada, comentaron sus experiencias en el proceso de dar soporte al tránsito social de sus hijos e hijas. Los datos fueron registrados en una videograbación y se procesaron mediante análisis de contenido y categorización. RESULTADOS: La transición social temprana tuvo beneficios positivos e inmediatos en el desarrollo del menor, además de en la disminución de la ansiedad. Hubo una mejora general en el humor, la autoestima y las relaciones tanto sociales como familiares. El acompañamiento de especialistas y asociaciones ayudó en las distintas situaciones sociales y favoreció la resiliencia. CONCLUSIONES: El tránsito social temprano es positivo en la esfera personal y sociofamiliar del menor. Para mejorar su resiliencia, las familias demandan acompañamiento en este proceso, así como conocer otras personas trans que les sirvan como referentes transpositivos. Además, señalan la necesidad de formación específica en los profesionales sanitarios.


Asunto(s)
Personas Transgénero , Transexualidad , Niño , Humanos , Menores , España , Padres , Investigación Cualitativa
19.
Nurs Rep ; 14(1): 42-55, 2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38251182

RESUMEN

BACKGROUND: University education is undergoing a paradigm shift towards active methodologies, such as virtual reality and training videos, which have proven to be valuable resources, especially in the health sciences. The scarcity of existing research on the topic prompted us to conduct this study, which seeks to measure the knowledge gained from the aforementioned tools by users, their level of satisfaction with them, and their perceived utility. METHODS: This is a quasi-experimental intervention study analysing the impact of virtual objects as learning resources for undergraduate nursing students. RESULTS: Fifty-four participants completed the training, yielding highly significant differences between their mean scores, with a high statistical power and a large effect size. A total of 85.46% of participants confirmed that the virtual resources helped them considerably to empathise with the experiences of trans people in healthcare settings. Students were comfortable using the virtual resources, very satisfied with the methodology employed, and would recommend the training received. CONCLUSIONS: University teaching must adapt to meet the current legislations and changing health needs of society, and teaching staff must be prepared to implement new active teaching methodologies that make learning a more dynamic process. Considering these results, our study serves as a guide for other nursing educators who seek to promote inclusive healthcare regarding gender diversity. This study is not registered.

20.
Adv Pharmacol Pharm Sci ; 2023: 1995642, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36776283

RESUMEN

Aims: To evaluate the prevalence and type of adverse drug reactions (ADRs), together with associated risk factors, among Cuban COVID-19 patients treated with chloroquine (CQ), lopinavir/ritonavir (LPV/r), or interferon α2b (IFN α2b), according to the Cuban protocol. Materials and Methods: A prospective descriptive analysis of ADRs was performed on 200 COVID-19 patients who were admitted consecutively to three hospitals in Havana and Pinar del Río from April to July 2020. Information on demographics, ADRs, outcomes, behavioral, and health-related factors was collected using a validated questionnaire and clinical records. Each potential ADR case was assessed for causality based on the WHO-UMC algorithm, concomitant drug influences, and the presence of any drug-drug interactions (DDI). Results: The total frequency of ADRs was 55%, with predominantly gastrointestinal disorders and general symptoms (23% vs 20%). 95.1% of ADRs occurred within 10 days after treatment and 42 potential DDI in 55.5% of patients (61/110) were observed. The prevalence of ADRs was: 44%, 30.4%, and 26.4% for IFN α2b, LPV/r, and CQ, respectively. Sex (odds ratio (OR): 0.40 (95% confidence interval (CI): 0.211-0.742), age (OR: 2.36 (95% CI: 1.02-5.44)), and underlying diseases (OR: 0.12 (95% CI: 0.06-0.23)) were independently associated factors for ADRs (P < 0.05). Conclusions: The frequency of ADRs and potential DDI was high compared to their use during nonpandemic times (e.g., for malaria, HIV, or inflammatory diseases). The safety profile of these drugs when used for COVID-19 treatment showed similar characteristics. Comorbidities, age >37 years old, and female sex were associated with ADRs.

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